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The present study investigated the infiltration of mast cells into the kidney tissue and the preventive role of mast cell stabilizers against high fat diet (HFD)-induced renal injury in rats. The animals were fed on HFD (30% fat) for 12 consecutive weeks to induce renal injury. The HFD-induced obesity was assessed by calculating obesity index, adiposity index, and estimation of total cholesterol, triglycerides, and high density lipoproteins in plasma. The renal dysfunction was evaluated by measuring creatinine clearance, blood urea nitrogen, uric acid, electrolytes and microproteinuria. The oxidative stress in renal tissues was determined by myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation and reduced glutathione level. The systolic blood pressure (SBP) was monitored using non-invasive blood pressure measuring apparatus. Histamine and hydroxyproline contents were quantified in renal tissues. Gross histopathological changes, mast cell density and collagen deposition in the renal tissue was determined by means of histopathology. The mast cell stabilizers, sodium cromoglycate and ketotifen were administered daily for 12 weeks. The HFD fed rats demonstrated significant increase in lipid profile, kidney injury with marked increase in renal oxidative stress, SBP, mast cell density, histamine content and hydroxyproline content that was attenuated by sodium cromoglycate and ketotifen treatment. Hence, the novel findings of this investigation suggest that HFD induced mast cells infiltration into kidney tissue seems to play an important role in renal pathology, and treatment with mast cell stabilizers serves as potential therapy in management of HFD induced renal dysfunction in rats.

The large number of plant-derived molecules have been explored in cancer cell lines and preclinical studies. As an outcome of these studies, decent number of isolated compounds expressed their candidature for being explored in clinical trials. The thrust behind development of plant-derived molecules is their low-cost and lesser side effects as compared to synthetic anticancer agents. Flavonoids are synthesized by plants as secondary metabolites and are a diverse chemical class possessing a wide spectrum of pharmacological activities such as anti-inflammatory, antiplatelet, antidiabetic, antimicrobial, cardioprotective, as well as anticancer activities. Various flavonoids especially genistein, myricetin, quercetin, luteolin, hesperidin, and epigallocatechin-3-gallate have been widely studied in cancer cell lines and animal models of tumorigenesis. In the recent past, the phase 1 and 2 clinical trials conducted with the aforementioned molecules have revealed promising results. Moreover, their supplementation reduced radiotherapy and chemotherapeutic agent-induced side effects in cancer patients. The present book chapter summarizes the subclasses of flavonoids with special reference to selected molecules from each class, which exhibited anticancer activity in cell lines and at present are being explored in various clinical trials.

It is well recognized that humans are enjoying longer life spans than their ancestors. However, longevity has resulted in a larger geriatric population worldwide, posing an enormous health care economic burden for treating age-related diseases such as neurodegenerative disorders, cardiovascular diseases, and cancer. The increased morbidity due to noncommunicable diseases (NCDs) often results in poor quality of life among elderly. Several theories have been proposed regarding the mechanisms of aging, but the exact mechanisms remain unknown. One proposed mechanism is oxidative stress theory causing damage to cell membrane and DNA from overproduction of reactive oxygen species and lack of antioxidants. Endogenous antioxidants and dietary antioxidants like vitamin A, C, and E, selenium, zinc, and copper contribute to antioxidant defense by quenching free radicals and inhibiting cellular lipid peroxidation and DNA damage. Functional foods rich in antioxidants and antiinflammation agents including omega-3 fatty acid, probiotics/prebiotics, and bioactive compounds have been found to have beneficial effects on the aging process and to mitigate the incidence of NCDs. Chromosomal telomere is considered a target site in the aging process as shortening of the telomere can cause senescence. External factors such as malnutrition smoking and sedentary lifestyle can negatively impact upon the aging process. Emerging evidence suggests that diets containing antioxidants and antiinflammatory agents can decrease oxidative stress and exert influence on epigenetic factors causing positive impact on longevity. Some dietary interventions have shown beneficial effect in animal models and humans. Mediterranean and Okinawa-type diets also promote good health and longevity. The intent of this review was to learn about the mechanisms involved in aging and to find ways that slow this process via dietary interventions and functional foods which help to promote healthy aging and longevity.

Flavonoids consist of a large family of polyphenolic molecules like flavones, flavonols, flavanols, isoflavones, flavanones, and anthocyanidins which are ubiquitously distributed in nature and are present in a wide array of plant products, including fruits, vegetables, and green tea. Because of their powerful antioxidant, anti-inflammatory, and anticancer properties, rigorous research is going on with a number of flavonoids (quercetin, quercitrin, rutin, morin, kaempferol, etc.) to investigate their disease-preventive and health-promoting benefits in humans. Several studies have shown that the cancer prevention and pharmacotherapeutic potential of different flavonoids depend on the type of flavonoid and its chemical structure, bioavailability, effective blood levels, and pharmacokinetic and pharmacodynamic characteristics. Many in vivo and in vitro studies conducted with different types of flavonoids have revealed diverse effects against different types of cancers. However, the major flavonoids (apigenin, luteolin, kaempferol) found in vegetarian diet have depicted limited possibility of curing cancer. In vitro studies done with apigenin and luteolin have shown effectiveness against cervical cancer cells, while kaempferol produced oncolytic effects against gastric and ovarian cancer cells. These flavonoids and their metabolites have revealed different anticancer effects due to their rapid metabolism in the small intestine and liver. Cancers comprise a group of noncommunicable diseases characterized by long-term debilitating illnesses that cause heavy burden on the healthcare system. At present, certain types of cancers are incurable, and palliative interventions are directed to delay the spread of malignant cancer and to ameliorate the painful episodes associated with cancer. The purpose of this review is to focus on the absorption, distribution, metabolism, and excretion (ADME) of different flavonoids and to evaluate the immune-boosting, cancer-preventive, and therapeutic potential of flavonoids against different types of cancers.

In recent years, the burden of several chronic diseases, including cancer, has increased rapidly worldwide. Although there are several diagnostic and treatment options available to health-care providers, the cancer-induced mortality rate is escalating globally. Interestingly enough, the development and utilization of plant-derived natural compounds therapy for the prevention and treatment of cancer are being rigorously pursued by overwhelming number of investigators. In the category of natural compounds, flavonoids occupy an important place and are being extensively studied in animal models and cancer patients to evaluate their anticancer potential. The chemopreventive role of flavonoids and their underlying mechanisms of action against cancer have been well documented in the literature. The present chapter summarizes the purported cellular, molecular, and genetic mechanisms of anticancer action of flavonoids, such as apoptosis induction, cell cycle arrest, anti-angiogenesis, anti-metastasis, and anti-inflammatory and antioxidant aspects. In addition, the anticancer roles of related flavonols (quercetin), flavones (luteolin), isoflavone (genistein), anthocyanidin (cyanidin), flavanone (naringenin), and flavan-3-ols (epigallocatechin-3-gallate) are also described.

Currently, type 2 diabetes is one of the most widespread noncommunicable maladies that inflict more than 400 million people globally. Diabetes-induced oxidative stress and distortion in gastrointestinal microbiota seem to play an important role in the occurrence of metabolic syndrome and related disorders. Oxidative stress causes imbalance between highly reactive oxygen species (ROS) and antioxidant systems of the body, resulting in metabolic syndrome, atherosclerosis, cardiovascular diseases, kidney problem, neuropathy, retinopathy, cancer risk, etc. Some studies show that imbalance in the gut microbiota also contributes in the development of type 2 diabetes. Microbial dysbiosis is considered to cause diabetic complications like cardiometabolic syndrome. Soluble dietary fibers have beneficial effects on gut microbiota and promote metabolic benefits on glucose control, but the underlying mechanisms remain unknown. Oral administration of purified and standardized phytopharmaceuticals containing bioactive compounds of different medicinal plants which help to normalize blood sugar level and promote healthy microbiota have proven useful in the prevention, mitigation, and management of diabetes as well as associated cardiometabolic syndrome. Recently, probiotics/prebiotics/synbiotics have gained importance in promoting healthy microbiota in diabetic patients. Probiotics consist of live bacteria present in foods like yogurt/cheese that confer health benefits on the host, while prebiotics are indigestible oligosaccharides that promote growth of beneficial bacteria in the gut. The focus of the review is to highlight the therapeutic potential of various types of phytomedicines and their known mechanistic actions involved in the management of type 2 diabetes. Results of clinical trials of herbal remedies and probiotics/prebiotics in humans and in vivo effects observed in animal models will also be described in this review. Randomized, placebo-controlled, and double-blind clinical studies with robust endpoints are needed for establishing the long-term safety, efficacy, and therapeutic relevance of phytopharmaceuticals and probiotics/ prebiotics/synbiotics in treating patients suffering from type 2 diabetes.

Background Inflammation-induced endothelial abnormalities, dietary habits, and tobacco smoking are considered to be the primary risk factors for causing atherosclerosis and Cardiovascular Diseases (CVDs), including Coronary Heart Disease (CHD), cerebrovascular disorders, peripheral arterial disease, rheumatic heart disease, congenital heart defects, deep vein thrombosis and pulmonary embolism. Prevention of CVDs with anti-inflammatory and anti-oxidant agents has been a challenging task for decades. Currently, CVDs have taken a top position among the health-related issues and are considered the foremost cause of mortality and morbidity around the globe. Objective Emerging evidence from several sources indicates that nutraceuticals and plant products may be a cost-effective approach for the prevention of CVDs. A limited number of clinical studies done with nutraceuticals have shown positive effects for promoting health and well-being as well as reduction of CVDs in humans. Some plants from which nutraceutical ingredients are isolated and will be discussed in this review are: Murraya koenigii, Curcuma longa, Beta vulgaris, Allium sativum, Allium cepa, Lagenaria siceraria Stand, Trigonella foenum-graecum. Methods Literature searches were done using keywords for plants, nutraceuticals, and plant products that have revealed beneficial effects in the prevention of CVDs. The anti-oxidant and anti-inflammatory actions of nutraceuticeuticals and plant ingredients play a significant role in capturing free radicals and reducing endothelial risk factors associated with the occurrence CVDs. Results This review has explored the usefulness of animal studies performed with nutraceuticals and herbal products and to understand their mode of action in the prevention of CVDs. Also, we have referred to patents for different nutraceuticals for better understanding their quantitative effects and dosage forms. Conclusion It is concluded that nutraceuticals possess enormous health benefits and their interventions can be highly beneficial in the prevention/reduction of CVDs and related disorders such as atherosclerosis, hypertension, heart attack and stroke. The findings of this review provide an update on the emerging uses of nutraceuticals, functional foods, and herbal remedies in humans. Nevertheless, large-scale randomized, placebo-controlled, double-blind clinical trials are needed to confirm the health benefit claims about nutraceuticals and herbal products to establish their long-term safety and to resolve the controversy about the role of clinical nutrition in curing lifestyle diseases.

Background: Human milk contains a number of nutrients and bioactive ingredients which play an important role in the growth and development of infants. One important nutrient and bioactive ingredient of human milk is L-tryptophan. L-Tryptophan is an essential aromatic α-amino acid and is required in the diet of children and adult humans. As an essential amino acid, it is needed for protein synthesis and as a precursor of key biomolecules such as serotonin, melatonin, tryptamine, niacin, quinolinic acid and kynurenic acid, nicotinamide adenine dinucleotide. The aim of the study was to evaluate the antioxidant, anti-inflammatory and antiproliferative properties of tryptophan isolated from enzymatic hydrolysates from human milk and its metabolites on human glioma U251 cells and to evaluate the effects of human recombinant (hrIFNγ) on molecular ions of tryptophan and its metabolites in human glial U251 cells. Methods: The cytotoxicity was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) assay. The antioxidant property was assessed by the oxygen radical scavenging capacity (ORAC) method. The anti-inflammatory effect was determined by the enzyme-linked immunosorbent assay (ELISA) against cytokines IL-6 and TNF-α. The effects of recombinant human (rhIFNγ) on molecular ions of tryptophan and its catabolites were evaluated by mass spectrometry. The tryptophan was isolated from milk peptides following enzymatic digestion, followed by separation by chromatographic and mass spectrometric methods. Results: Tryptophan from human milk exhibited profoundly higher oxygen radical absorption capacity (7,986±468 µm Trolox equivalent (TE)/g) than that of whole human milk (80.4±13.3 µm TE/g). Tryptophan showed a moderate degree of anti-inflammatory activity against TNF-α and IL-6. rhIFNγ inhibited tryptophan metabolism. A low concentration of L-tryptophan (10–25 μg/mL) inhibited nearly 25% of cell growth. When U251 cells were treated with 25 μg/mL L-tryptophan and subsequently challenged with 30 ng/mL of human recombinant IFNγ, a significant inhibitory effect on cell growth was observed. Low concentrations of Xanthurenic acid, L-kynurenine, and 3-OH DL kynurenine were found to inhibit cell growth except melatonin and 3-OH anthranilic acid. Melatonin was a strong inducer of TNF-α in RAW cells, whereas 3-OH kynurenine at 25, 50 and 100 µg/mL inhibited IL-6 in RAW cells. No significant change was observed in the IL-8 profile in tryptophan-treated U251 cells except that L-kynurenine at 10 µg/mL produced significantly high level of an inflammatory cytokine IL-8. Melatonin, 3-OH, DL kynurenine at high concentrations (100 µg/mL) induced proliferation of U251 cells. Melatonin seemed to show synergistic effects with recombinant human IFNγ (rhINFγ) in promoting growth of human glioma cells. While treatment of U251 cells with tryptophan alone and subsequent treatment with rhIFNγ inhibited the growth of human cancer glioma cells, and conversely melatonin combined with rhIFNγ promoted growth of the U251 cells. Conclusions: The findings from this study suggest that human milk-derived tryptophan and its metabolites possess strong antioxidant properties. Such effects might play a significant role in regulating the cell proliferation and growth of human cancer cells in a concentration-dependent manner.

Background The prevalence of mental depression has increased in recent years, and has become a serious health problem in most countries of the world, including India. Due to the high cost of antidepressant synthetic drugs and their accompanying side effects, the discovery of safer antidepressant herbal remedies is on the rise. Moringa oleifera (MO) (drumstick) has been used in traditional folk medicine, and in Ayurveda, it is considered as a valuable remedy for treating nervous system disorders as well as memory enhancing agent. Objective The present study was designed to evaluate the acute and chronic behavioral and antidepressant effects of alcoholic extracts of MO leaves in standardized mouse models of depression. Materials and methods Alcoholic extracts of MO (MOE) leaves were prepared, and phytoconstituents were determined using appropriate chemical analytical methods. Following preliminary dose-finding toxicity studies, the biological activity of MOE was tested in Swiss albino mice. Animals were divided into six groups: Groups 1 and 2 served as vehicle control and fluoxetine (20 mg/kg) standard control, respectively. Groups 3 and 4 served as treatment groups and were orally administered ethanolic MOE at doses of 100 mg/kg and 200 mg/kg, respectively. Groups 5 and 6, respectively, received combination doses of MOE 100 mg/kg + 10 mg fluoxetine, and MOE 200 mg/kg + 10 mg/kg fluoxetine. Following acute and 14 days chronic treatments, all animals were tested using behavioral models of depression, such as forced swim test (FST), tail suspension test (TST), and locomotor activity test (LAT). Results Significant changes in all tested activities (FST, TST, LAT) of chronically dosed mice were observed, especially in animals given simultaneously combined doses of 200 mg/kg/day MOE + 10 mg/kg/day fluoxetine for 14 days. The antidepressant effect of MOE may have been invoked through the noradrenergic-serotonergic neurotransmission pathway, which is the hallmark of selective serotonin reuptake inhibitors (SSRI) class of drugs. Conclusion The results obtained in this study suggest that combined administration of MOE with low doses of fluoxetine or other SSRI drugs seems to have promising potential.

There is evidence that optimal nutrition is fundamental to human health and in the prevention of non-communicable diseases (NCDs) later in adult life. The identification, production and consumption of functional foods worldwide can increase health benefits for all who can access and afford such foods subject to advice from nutritionists. Recent meetings organized by the health agencies, give a crucial opportunity to make nutrition, a central part of the post-2015 sustainable human and agricultural development agenda. The aim of discussions in these meetings was to provide functional crops and foods to achieve optimal health by prevention of NCDs. It is possible that these efforts might ensure that the goals and targets set in the agenda are adequate to address the many challenges of global undernutrition as well as obesity which are major risk factors of NCDs. In many developing and middle income countries, food security provided by the governments, in one sense understandably, gave least consideration to functional foods supply and the prevention of obesity and metabolic syndrome, resulting in to emergence of NCDs. The Thailand Declaration reiterates that commitments to eradicate hunger and undernutrition as well as over-nutrition, and to increase investments in effective interventions; designers foods and designers crops. However, in planning coherent policies, our past experience on rapidly absorbed, energy-rich processed foods should be taken in to account while developing sustainable food systems. The food industry should be educated to exploit the expertise of food scientists and health professionals in designing functional foods taking cognizance of manufacturing and processing. Similarly, agriculture scientists may be actively involved in educating farmers so as to grow cash crops providing functional foods. The aim should be to achieve an increase in the availability of functional foods to an extent, or by a policy, by which such foods are available to poors, at affordable cost to prevent hunger and undernutrition and related diseases as well as NCDs. In addition our efforts might help in developing an international consensus on how to approach the development of new designer foods by farmers and food industry to produce low glycemic index foods. Such efforts may establish an international framework for the prevention of NCDs, so that human susceptibility to these diseases is substantially diminished.

Alcohol appears to be a double-edged sword because moderate alcohol intake is protective whereas drinking more than 10 drinks in a week appears to have adverse effects on morbidity and mortality. Recently, the exponential nature of the relation between average alcohol consumption and mortality has been demonstrated in Russia. This study revealed that substantial numbers of people report drinking three or more half-litre bottles of vodka per week. However, the exponential curves for dose-response relations between average volume of alcohol consumption and the mortality risk of various diseases is not fully explained. The variation in mortality may be due to presence of confounders such as physical activity, greater consumption of fish and salads which are rich sources of omega-3 fatty acids and polyphenolics. It is possible that patients with type 2 diabetes, moderate alcohol us-e, particularly wine consumption, is associated with reduced risks of cardiovascular events and all-cause mortality. Serge C. Renaud gave the definition of the French paradox and suggested that the inhibition of platelet reactivity by wine may be one explanation for protection from CAD in France. It is known that aging of alcohol also increases 1, 1-diphenyl-2-picrylhydrazyl radical scavenging activity and therefore moderate drinking of aged whisky and other alcoholic drinks in moderation may provide beneficial effects. Excess of alcohol intake causes decreases in vitamin B1, B6 and B12 as well as in folic acid, antioxidants vitamins A,E ,C and beta carotene, flavonoids, amino acids, coenzyme Q10, l-carnitine, omega-3 fatty acids as well as in minerals magnesium, potassium, calcium, copper, zinc, chromium and selenium. Alcoholism also has a direct adverse effects on cell membrane, mitochondria and genes. Alcoholic cirrhosis, fatty liver, cardiomyopathy, hypertriglyceridemia, hyperuricemia, oxidative stress and inflammation are well known adverse effects of alcoholism. It also damages the brain causing dementia, depression and psychosis. However, moderate alcohol intake up to 10 drinks per week may have beneficial effects on the risk of all these problems. Moderate alcohol intake increases HDL-C, and decreases C-reactive proteins, IL-6, TNF-alpha, Lp (a), plasminogen activator inhibiter-1, insulin resistance which are risk markers of CVDs, type 2 diabetes and cancer. These beneficial effects are enhanced by omega-3 fatty acids and polyphenolics that are rich in Mediterranean style diets. Vodka and spirits can be made healthly if enriched with fish oil or alpha- linolenic acid (rich source of w-3) and cocoa (flavanol) which can repair this deficiency. It is like a cleaning drink for the all the organs of the body. If standard Vodka is 40% alcohol, then we need +/- 1-g DHA per 500-ml bottle.

Colostrum is a thick, sticky, yellowish mammary secretion that all mammals provide to their newborns during the first 24–48 hours after delivery. Human newborns receive colostrum from their mothers during the first few hours after birth, and this “Elixir of Life” not only provides naturally produced nutrients and antibodies in a highly concentrated low volume but also creates the foundation of life-long immunity. Colostrum is rich in immunoglobulins and lactoferrin, growth, and antimicrobial factors, all of which promote tissue growth and maturation of digestive tract and immune function in neonatal animals and humans. The immunoglobulins present in colostrum invoke antimicrobial activity by forming a chelated complex with bacterial and viral antigens. It has been reported that constituents from bovine colostrum (BC) are 100-fold to 1000-fold more potent than human colostrum. This means that if the human neonates do not get enough maternal colostrum to build their passive immunity, then they can rely on cow or buffalo colostrum to gain health benefits. There is emerging evidence that BC may be one of the promising nutraceuticals which can prevent or mitigate various diseases in newborns and adults. Immunity-related disorders are one of the leading causes of morbidity in the world. BC has the potential to enhance the immune function and well-being of healthy persons and patients. The immunoglobulins and lactoferrin present in colostrum are known to build natural immunity in newborns, which helps to reduce the mortality rate in this population. Lactoferrin is involved in several physiological and protective functions, including regulation of iron absorption in the bowel, antioxidant, anticancer, antiinflammatory, and antimicrobial activities. As opposed to milk, BC has less lactose, and therefore may be suitable for patients suffering from lactose intolerance. A limited number of human and animal studies done with colostrum supplements are indicative of future prospects for helping in curing diseases like AIDS, cardiovascular and gastrointestinal disorders, infectious diseases, wound healing, and certain cancers. Since colostrum has several naturally occurring important nutritional components, well-designed, double-blind, placebo-controlled studies with colostrum products are needed to widen their therapeutic role in children and adults. It indeed seems to be a treasure trove that, if tapped, could eventually reveal many health benefits and cost-effective cures in humans. This review summarizes the comparative amounts of fat, proteins, lactose, vitamins, and minerals present in human, cow, buffalo, and goat colostrum. The major objectives of this review are to create awareness about the nutraceutical properties of colostrum, and to discuss the various ongoing alternative treatments of colostrum and its active ingredients as well as to address colostrum’s future nutraceutical and therapeutic intervention in humans.

The present study investigated the role of N-methyl-d-aspartate (NMDA) receptors in curcumin-mediated renoprotection against ischemia reperfusion (I/R)-induced acute kidney injury (AKI) in rats.Rats were subjected to bilateral renal I/R (40 min I, 24 hours R) to induce AKI. Kidney injury was assessed by measuring creatinine clearance, blood urea nitrogen, plasma uric acid, potassium level, fractional excretion of sodium, and macroproteinuria. Oxidative stress in renal tissues was assessed by measuring myeloperoxidase activity, thiobarbituric acid reactive substances, superoxide anion generation, and reduced glutathione content. Hematoxylineosin staining was done to assess histological changes in renal tissues. Curcumin (30 and 60 mg/kg) was administered one hour before subjecting rats to AKI. In separate groups, NMDA receptor agonists, glutamic acid (200 mg/kg), and spermidine (20 mg/kg) were administered prior to curcumin treatment in rats followed by AKI.I/R-induced AKI was demonstrated by significant change in plasma and urine parameters along with marked increase in oxidative stress and histological changes in renal tissues that were aggravated with pretreatment of glutamic acid and spermidine in rats. Administration of curcumin resulted in significant protection against AKI. However, glutamic acid and spermidine pretreatments prevented curcumin-mediated renoprotection.It is concluded that NMDA receptor antagonism significantly contributes towards curcumin-mediated protection against I/R-induced AKI.

Erectile dysfunction (ED) or male impotence is defined as inability of a man to achieve or maintain penile erection sufficient for sexual activity. It is primarily a neuronal and endothelial dysfunction of the corpus cavernosum of penile tissue, and is partly characterized by reduced production of nitric oxide (NO). Other factors that may contribute to the pathogenesis of ED include androgen deficiency in aging men, hypertension, high cholesterol levels, atherosclerosis, diabetes mellitus, diseases of the prostate and heart, and anatomical deformity of the penis. ED may also be caused by some medications, prostate surgery and spinal cord injury. Psychological and social conditions such as stress, depression and unhappy marital relationship may contribute to the problem. Chronic infections and inflammation can also contribute to the disease process. ED is linked to an increased risk for cardiovascular diseases and stroke. Several orally active drugs (sildenafil, vardenafil, tadalafil, avanafil) are currently prescribed for treating ED to improve the arterial blood flow to the penile tissue. Medicinal plants and their extracts have been used in traditional medicine in southwest Asia and other countries to treat ED. The current review focuses on four medicinal plants that have been used as aphrodisiacs for enhancing sexual performance and for the treatment of ED. These plants include Eurycoma longifolia Jack (tongkat ali); Chlorophytum borivilianum (safed musli); Withania somnifera (ashwagandha); and Pausinystalia johimbe (formerly known as Corynanthe johimbe). Suggested mechanisms of action for each of the plant extracts will be discussed.

Dipyridamole (DYP) is an anti-platelet agent with marked vasodilator, anti-oxidant, and anti-inflammatory activity. The present study investigated the role of adenosine receptors in DYP-mediated protection against ischemia reperfusion-induced acute kidney injury (AKI) in rats. The rats were subjected to bilateral renal ischemia for 40 min followed by reperfusion for 24 h. The renal damage induced by ischemia reperfusion injury (IRI) was assessed by measuring creatinine clearance, blood urea nitrogen, uric acid, plasma potassium, fractional excretion of sodium, and microproteinuria in rats. The oxidative stress in renal tissues was assessed by quantification of thiobarbituric acid-reactive substances, superoxide anion generation, and reduced glutathione level. The hematoxylin-eosin staining was carried out to observe histopathological changes in renal tissues. DYP (10 and 30 mg/kg, intraperitoneal, i.p.) was administered 30 min before subjecting the rats to renal IRI. In separate groups, caffeine (50 mg/kg, i.p.), an adenosinergic A1 and A2A receptor antagonist was administered with and without DYP treatment before subjecting the rats to renal IRI. The ischemia reperfusion-induced AKI was demonstrated by significant changes in serum as well as urinary parameters, enhanced oxidative stress, and histopathological changes in renal tissues. The administration of DYP demonstrated protection against AKI. The prior treatment with caffeine abolished DYP-mediated reno-protection suggesting role of A1 and A2A adenosine receptors in DYP-mediated reno-protection in rats. It is concluded that adenosine receptors find their definite involvement in DYP-mediated anti-oxidative and reno-protective effect against ischemia reperfusion-induced AKI.

Background Fibrous structures and synthetic polymer blends offer potential usages in making biomedical devices, textiles used in medical practices, food packaging, tissue engineering, environmental applications and biomedical arena. These products are also excellent candidates for building scaffolds to grow stem cells for implantation, to make tissue engineering grafts, to make stents to open up blood vessels caused by atherosclerosis or narrowed by blood clots, for drug delivery systems for micro- to nano-medicines, for transdermal patches, and for healing of wounds and burn care. The current study was designed to evaluate the antimicrobial activity of woven and non-woven forms of nano- and macro-scale blended polymers having biocompatible and biodegradable characteristics. Methods The antimicrobial activity of non-woven fibrous structures created with the combination of synthetic and biopolymer was assessed using Gram-negative, Gram-positive bacteria, such as Staphylococcus aureus, Proteus vulgaris, Escherichia coli and Enterobacter aerogenes using pour plate method. Structural evaluation of the fabricated samples was performed by Fourier transform infrared spectroscopy. Results Broad spectrum antibacterial activities were found from the tested materials consisting of polyvinyl alcohol (PVA) with chitosan and nylon-6 combined with chitosan and formic acid. Conclusions The combination of PVA with chitosan was more bactericidal or bacteriostatic than that of nylon-6 combined with chitosan and formic acid. PVA combination with chitosan appears to be a broad-spectrum antimicrobial agent.

BACKGROUND The present study was designed to examine the anti-inflammatory effects of plant-derived products marketed for human health benefits. METHODS The tumor necrotic factor-α (TNF-α) was used as a proinflammatory biomarker generated by mouse macrophage RAW 264.6 cells. The in vitro tested plant products include Saskatoon berry (SKB), quercetin, purified oat beta-glucan (OBG), curcumin, and turmeric. Quantification of TNF-α in cell culture supernatants was carried out using mouse TNF-α assay kit and the cell proliferation was determined by MTT (3-(4, 5-dimethylthiazolyl-2)-2,5- diphenyltetrazolium bromide) assay. The cells were grown in Dulbecco's modified Eagle's medium supplemented with 10% heat-inactivated fetal bovine serum and 100 U/mL penicillin and 100 µg/mL streptomycin. Bacterial lipopolysaccharide (LPS) at a concentration of 500 ng/mL was employed to stimulate the TNF-α production in mouse macrophage cells. RESULTS Results showed that curcumin at 10 µM (3.7 µg/mL) level effectively attenuated the LPS-induced inflammatory response, and at 100 µM completely inhibited macrophage RAW cell growth (p

Nutraceutical, a term combining the words “nutrition” and “pharmaceuticals”, is a food or food product that provides health benefits as an adjuvant or alternative therapy, including the treatment and prevention of infectious diseases in children and adults. There is emerging evidence that bovine colostrum (BC) may be one of the promising nutraceuticals which can prevent or mitigate various diseases in newborns and adults. Immunity-related disorders are one of the leading causes of mortality in the world. BC is rich in immunity, growth and antimicrobial factors, which promote tissue growth and the maturation of digestive tract and immune function in neonatal animals and humans. The immunoglobulins and lactoferrin present in colostrum are known to build natural immunity in newborns which helps to reduce the mortality rate in this population. Also, the side-effect profile of colostrum proteins and possible lactose intolerance is relatively less in comparison with milk. In general, BC is considered safe and well tolerated. Since colostrum has several important nutritional constituents, well-designed, double-blind, placebo-controlled studies with colostrum products should be conducted to widen its therapeutic use. The objectives of this review are to create awareness about the nutraceutical properties of colostrum and to discuss the various ongoing alternative treatments of colostrum and its active ingredients as well as to address colostrum’s future nutraceutical and therapeutic implications in humans.

This overview was directed towards understanding the relationship of brain functions with dietary choices mainly by older humans. This included food color, flavor, and aroma, as they relate to dietary sufficiency or the association of antioxidants with neurodegenerative diseases such as dementia and Alzheimer’s disease. Impairment of olfactory and gustatory function in relation to these diseases was also explored. The role of functional foods was considered as a potential treatment of dementia and Alzheimer’s disease through inhibition of acetylcholinesterase as well as similar treatments based on herbs, spices and antioxidants therein. The importance of antioxidants for maintaining the physiological functions of liver, kidney, digestive system, and prevention of cardiovascular diseases and cancer has also been highlighted. Detailed discussion was focused on health promotion of the older person through the frequency and patterns of dietary intake, and a human ecology framework to estimate adverse risk factors for health. Finally, the role of the food industry, mass media, and apps were explored for today’s new older person generation.

Despite overwhelming and tragic evidence of their detrimental and dangerous consequences, amphetamines remain significant drugs of abuse and addiction. The effects of 4-substituted amphetamines: 4-hydroxyamphetamine (4-HA), 4-methoxyamphetamine (4-MEA), 4-ethoxyamphetamine (4-ETA), 4-propoxyamphetamine (4-PPA), and 4-benzyloxyamphetamine (4-BEA) on intrauterine development, pregnancy outcome, postnatal growth, and survival were compared in Swiss-Webster mice. Single daily doses (0, 50,or 100 mg/kg) of an aqueous solution of different amphetamines were administered on pregnancy days 6 through 18. The 50 mg/kg doses of all amphetamines were well tolerated by the mothers and did not produce any overt signs of maternal toxicity or death. However, a few mothers died on different days of gestation after receiving 100 mg/kg of 4-HA, 4-MEA, 4-ETA, and 4-BEA. The mothers that failed to deliver naturally (3 d after the due date) were killed and their uteri were examined for live/dead fetuses and resorption sites. In comparison with respective controls, the incidence of resorptions was markedly higher in the 4-MEA- and 4-ETA-dosed groups. Delivery was prolonged in the 4-PPA- and 4-BEA-treated dams. Apparently well-formed but dead pups were delivered by 4-HA-, 4-PPA-, and 4-BEA-dosed mice. Marked reductions in average litter size and weight occurred after intrauterine exposure to 100 mg/kg 4-BEA. Treatment with 4-ETA, 4-PPA, and 4-BEA not only resulted in a high incidence of cannibalism within 24 h after birth but also caused an increase in cumulative pup mortality during the first 3 weeks of age. Body weight gain was significantly lower in 3-week-old offspring exposed to 4-HA and 4-PPA than in the controls. The findings suggest that 4-substituted amphetamines exhibit a wide variation in their effects on maternal toxicity and pregnancy wastage, and produce adverse effects on parturition, pup survival, and postnatal development.

Mediterranean-style diets caused a significant decline in cardiovascular diseases (CVDs) in early landmark studies. The effect of a traditional Mediterranean diet on lipoprotein oxidation showed that there was a significant reduction in oxidative stress in the intervention group (Mediterranean diet + Virgin Olive Oil) compared to the low-fat diet group. Conversely, the increase in oxidative stress causing inflammation is a unifying hypothesis for predisposing people to atherosclerosis, carcinogenesis, and osteoporosis. The impact of antioxidants and anti-inflammatory agents on cancer and cardiovascular disease, and the interventive mechanisms for the inhibition of proliferation, inflammation, invasion, metastasis, and activation of apoptosis were explored. Following the Great Oxygen Event some 2.3 billion years ago, organisms have needed antioxidants to survive. Natural products in food preservatives are preferable to synthetic compounds due to their lower volatility and stability and generally higher antioxidant potential. Free radicals, reactive oxygen species, antioxidants, pro-oxidants and inflammation are described with examples of free radical damage based on the hydroxyl, nitric oxide and superoxide radicals. Flavonoid antioxidants with 2- or 3-phenylchroman structures such as quercetin, kaempferol, myricetin, apigenin, and luteolin, constituents of fruits, vegetables, tea, and wine, which may reduce coronary disease and cancer, are described. The protective effect of flavonoids on the DNA damage caused by hydroxyl radicals through chelation is an important mechanism, though the converse may be possible, e.g., quercetin. The antioxidant properties of carotenoids, which are dietary natural pigments, have been studied in relation to breast cancer risk and an inverse association was found with plasma concentrations: higher levels mean lower risk. The manipulation of primary and secondary human metabolomes derived especially from existing or transformed gut microbiota was explored as a possible alternative to single-agent dietary interventions for cancer and cardiovascular disease. Sustained oxidative stress leading to inflammation and thence to possibly to cancer and cardiovascular disease is described for spices and herbs, using curcumin as an example of an intervention, based on activation of transcription factors which suggest that oxidative stress, chronic inflammation, and cancer are closely linked.

Human peripheral blood mononuclear leukocytes (PBML) proliferation was measured in the presence or absence of amphetamines. Proliferation in response to T-cell mitogen PHA was suppressed from 22 to 34% by d- and dl-amphetamine, respectively, contrarily to 1-form which did not affect proliferation of PHA-stimulated PBML. The ‘designer’ amphetamines appeared to be more potent inhibitors of PBML proliferation induced by both PHA and PWM stimulation than those of the racemic and isomeric forms of amphetamine. A wide variation was seen in the suppressive actions of the ‘designer’ amphetamines, and the mean percentages of suppression varied from 12 to 45% compared with the control values. 4-Propoxyam-phetamine (4-PA) was found to be the most active among the ‘designer’ drugs. In vitro effects of d-, 1- and dl-amphetamine were also studied on natural killer (NK) cell activity. A marked increase in the NK cell activity was observed only in the presence of very low concentrations (10−12 to 10−10 M) of dl-amphetamine, however, the activity of the NK cell remained within the control limits in the presence of d- or 1-forms. The findings suggest that the abuse of amphetamines, especially the ‘designer’ drugs, may adversely affect the activity of immunoregulatory cells and might lead to a compromised immune system in amphetamine abusers.

Recently, drug interactions with grapefruit juice (GFJ) have received considerable attention from basic scientists, physicians, industry and drug regulatory agencies. GFJ has been shown to inhibit cytochrome P-450 3A4 isoenzyme and P-glycoprotein transporters in the intestine and liver. The GFJ-induced inhibitory effects are considered to be responsible for alterations in drug bioavailability, and pharmacokinetic and pharmacodynamic changes when drugs are ingested concurrently with GFJ. However, little or no interaction is observed when GFJ is taken concomitantly with parentally administered drugs. It is well known that risk factors for cardiovascular disease increase with advancing age, while hepatic metabolic activity decreases in elderly individuals. It is, therefore, possible that the combination of GFJ and cardiovascular medications may pose a health risk, especially in elderly patients. A number of studies have shown interactions of GFJ with cardiovascular drugs such as calcium-channel blockers, angiotensin II receptor antagonists, beta-blockers, and statins. Such interactions are likely to change the pharmacokinetics and pharmacodynamics of these drugs, consequently causing undesirable health effects. Therefore, health care professionals and the public need to be advised of the potential risks associated with the concomitant use of GFJ and interacting medications, especially cardiovascular drugs and agents with a narrow therapeutic index. This review focuses on the adverse interactions of GFJ and cardiovascular medications, and the proposed underlying mechanisms of such interactions.

Hypertension, myocardial infarction, atherosclerosis, arrhythmias and valvular heart disease, coagulopathies and stroke, collectively known as cardiovascular diseases (CVDs), contribute greatly to the mortality, morbidity and economic burden of illness in Canada and in other countries. It has been estimated that over four million Canadians have high blood pressure, a comorbid condition that doubles or triples the risk of CVD. According to the Heart and Stroke Foundation of Canada, CVDs caused 36% of deaths in 2001 and were responsible for 18% of the total hospital costs in Canada. The majority of Canadians exhibit at least one CVD-related risk factor, such as tobacco smoking, physical inactivity, diabetes, obesity, hypertension, a lack of daily fruit and vegetable consumption, and psychosocial factors, making these people more prone to developing a serious CVD-related illness in the future. It is therefore important that CVD-related causes and concerns be addressed. Given the scope and prevalence of CVDs, it is obvious that a population health approach – ‘prevention is better than cure’ – would be the most appropriate model to adopt to deal with this ubiquitous health problem and to reduce the costs of hospitalization, long-term medication and rehabilitation. The focus of the present review is to evaluate and compare the results of epidemiological, experimental and clinical studies, reporting on the influence of physical activity, dietary intervention, obesity and cigarette smoking on cardiovascular health and the prevention of CVDs. The prophylactic measures must be dealt with collectively because there is overwhelming evidence that the occurrence of CVDs can be reduced by approximately 80% by making lifestyle modifications. The preventive strategies against CVDs must be targeted at a primary health promotion level before some of the important underlying causes of CVD seriously afflict a person or a population at large. Such preventive approaches would help in reducing not only employee absenteeism but also the hospital and drug costs burdening the health care systems of both developed and developing countries.

Herbal and plant based remedies have been used since times immemorial for treating illnesses or maladies of variant aetiology, whereas during the past two centuries, the pharmaceutical chemists have discovered many important modern drugs from natural botanicals and microbes. Generally, herbal and plant-derived products containing multiple compounds are administered orally for therapeutic purposes. Currently, targeted drug-delivery systems are being developed and investigated for the treatment of cardio-respiratory disorders, pain relief, wound healing, and life threatening diseases like cancers. A number of novel nanofiber membranes and devices are available for sustained release and to deliver steady supply of natural bioactive ingredients, herbal-based extracts, and a few have been approved by US-FDA and other drug regulatory agencies. The purpose of this mini review is to provide an update on the role of nanofiber devices used for the targeted-delivery of therapeutically active ingredients of plant and herbal origin as well as to underscore the potential for the delivery of cost-effective herbal ingredients and natural plant-based extracts for their biomedical applications in wound healing, inflammation-related diseases and cancer treatment. Biomed Rev 2015; 26: 37-42. Key words: targeted-delivery, natural botanicals, plant-derived ingredients, nanofibrous medical devices, biodegradable and biocompatible polymers

Nanotechnology is rapidly advancing and will leave no field untouched by its ground breaking innovations. Nanoparticles are molecules with a diameter ranging from 10-100 nm. Nanotechnology has promising biomedical applications and most noteworthy amongst them are noble metal particles. For instance, gold nanoparticles (AuNPs) provide a unique blend of physical and optical properties, chemical inertness, and high surface to volume ratio. They can be synthesized as well as functionalised to support various ligands on their surface. Their surface functionalization and diverse properties render the gold nanoparticles highly useful for drug delivery and gene carrier for therapeutic purposes and as molecular probes for disease diagnosis. The foundation for the usage of AuNPs in therapeutics and diagnosis was laid by the ancient studies done with ruby gold for curing diseases in middle ages. Presently, AuNPs have become available in different types such as spheres, rods, shells, cages and SERS particles which vary in shape, size and physical properties. The biomedical applications of these particles include drug and gene delivery, cancer diagnosis and therapy, determination of biological molecules and microorganisms, detection of disease etiology, immunoassay, enzyme immobilization, etc. Overall, the focus of this review is to highlight that AuNPs provide an excellent platform for the discovery of new therapies, cure for certain cancers, molecular probe for diagnostic purposes, as well as gene carriers and drug delivery vehicles. Biomed Rev 2015; 26: 23-36. Key words: gold nanoparticles, cancer treatment, drug delivery system, gold nanocarrier therapy

Since the initial observations over 25 years ago thatalcohol (ethanol) is a human teratogen (Jones andSmith, ’73; Jones et al., ’73), concerns regarding theprenatal effects of alcohol as a significant public healthproblem have been raised throughout the world. Mucheffort has gone into the delineation of a physical andneurobehavioral phenotype, numerous studies have fo-cused on the birth prevalence of those phenotypes invarious populations, and countless experiments havedocumented the prenatal effects of alcohol in a varietyof animal species. Investigations into the risks of drink-ing small and moderate amounts of alcohol duringpregnancy have been undertaken, education and pre-vention campaigns have been implemented, and pro-grams to benefit affected children have been estab-lished.Although there are numerous gaps in knowledgewhen considering the full spectrum of effects of pre-natal exposure to alcohol, several unresolved prob-lems relating to the diagnosis and prevention of themost severe end of the spectrum, fetal alcohol syn-drome (FAS), are of particular importance. The fol-lowing five points describe these issues and the Pub-lic Affairs Committee’s recommendations in responseto each.

Lactose intolerance is a common disorder affecting an individual's ability to digest lactose present in milk or any food product. Lactose intolerance is caused by the deficiency of β-galactosidase (lactase) in the digestive tract. Diagnosis of lactose intolerance is not so simple and straightforward clinically. Many biochemical and genetic tests have been developed for the determination of lactose intolerance. Several case reports indicate wherein subjects have self-diagnosed being lactose intolerant. There is an emerging link of this disorder with human gene polymorphism, where genetic basis has been used as a diagnostic tool. The high prevalence of this condition among children and adults has compelled the production of lactose-free foods. Additionally, external enzyme supplementation has been looked at as an alternative protective mechanism in lactose intolerant subjects. This review highlights the genetic variants of lactase polymorphism and theranostic (therapeutic and diagnostic) strategies for lactose intolerance. Biomedical Reviews 2014; 25: 35-44.

Celiac disease (CD) is one of the most common inflammatory diseases of the small intestine which causes abdominal pain, diarrhoea, malabsorption, weight loss, anorexia, and iron deficiency anaemia in humans. It is a human leukocyte antigen (HLA)-linked disorder that is triggered by the gluten and gliadin proteins from wheat and related cereals. The presence of other genetic factors such as HLA-DQ2 and HLA-DQ8 have also been identified for the generation of circulating autoantibodies to the enzyme transglutaminase (TG2). The TG2 enzyme deamidates the gluten peptides and increases their affinity for the HLA-DQ2 or HLA-DQ8, which in turn cause a more vigorous activation of CD4+ T-helper 1 (Th1) cells and trigger the immune response, and such immune cascade eventually leads to intestinal membrane damage and malabsorption. Generally, CD is managed by lifelong gluten-free diet. However, strict adherence to a gluten-free diet is difficult and is not always effective. Several pharmacological agents and alternative therapies for treating CD are currently under development and are in clinical trials, The purpose of this review is to highlight the complex involvement of genetics and immunity in CD and to focus on the novel strategies being used for developing adjunct and alternative therapies for the treatment of CD. Biomedical Reviews 2014; 25: 45-58.

The renin-angiotensin system is associated with a variety of pathophysiological processes in many organ systems, and is known to be involved in the normal regulation of blood pressure and in the pathogenesis of renovascular hypertension. Angiotensin II is a multifunctional hormone that manifests its properties by interacting with two major subtypes of cell surface receptors (AT1 and AT2). Angiotensin converting enzyme (ACE) inhibitors are able to modify the actions of the renin-angiotensin system, and are indicated for the treatment of hypertension and heart disease. The antihypertensive effects of ACE inhibiting drugs are related to their ability to block the conversion of the decapeptide, angiotensin I, to the potent pressor octapeptide, angiotensin II. ACE inhibitors have been implicated in fetopathies in humans and perinatal mortality in rats, rabbits, sheep and baboons. Human fetopathies were seen when ACE inhibitors were given around the 26th week of gestation. The major adverse effects in babies include: oligohydramnios, renal tubular dysgenesis, neonatal anuria, calvarial and pulmonary hypoplasia, mild to severe intrauterine growth retardation, persistent patent ductus arteriosus and fetal or neonatal death. These developmental anomalies are thought to be partly due to a direct action of ACE inhibitors on the fetal renin-angiotensin system and partly due to the ischemia resulting from maternal hypotension and decreases in fetal-placental blood flow and oxygen/nutrient delivery to the fetus. The purpose of this review is to briefly discuss the pathophysiological role of the renin-angiotensin system, the therapeutic uses of ACE inhibitors in pregnant patients and to focus primarily on the major fetotoxic effects of ACE inhibitors encountered in humans and animal models. I will also review our recent data which show that capozide (captopril + hydrochlorothiazide) not only produces oligohydramnios but also disturbs the balance of glucose and NaCl in the maternal plasma and amniotic fluid of the rat.

(i) The urinary elimination of methoxyphenamine (MPA) and its metabolites in underivatized samples was examined after single and multiple oral administration to pregnant and non-pregnant mice by GLC and GLC—MS. (ii) The major metabolite O-desmethylmethoxyphenamine (ODMP), along with lesser amounts of N-desmethylmethoxyphenamine (NDMP) and 2-hydroxyamphetamine (2OH), were the only metabolites detected in urine extracts of pregnant and non-pregnant mice. 5-Hydroxymethoxyphenamine (5HMP) was not detected. Enzyme hydrolysis did not increase the recovery of either substrate or metabolites in either the pregnant or non-pregnant animals. The results show that MPA metabolism in the Swiss—Webster mouse is distinctly different from that seen in man and other laboratory animals. (iii) The mean MPA:ODMP ratio in day-6 urine from pregnant mice after a single dose was 0.31 ± 0.04. The NDMP:ODMP ratios were less than 0.10 in all samples. Non-pregnant mice urine had equivalent amounts of MPA, NDMP, ODMP, and 2OH after multiple dosing. (iv) While multiple dosing and pregnancy did not alter either the urinary recovery or profile of the metabolites detected, there was a linear decrease in the MPA:ODMP ratio during gestation. (v) MPA was extensively metabolized to ODMP in the male mice, and the MPA:ODMP ratio of 0.41 was slightly higher than that observed in the pregnant and non-pregnant females.

The urinary elimination of 4-hydroxyamphetamine (PHA) and a series of homologous 4-alkoxy-substituted amphetamines and their metabolites was examined after single and multiple oral administration to pregnant and non-pregnant mice. The metabolic profile and extent of biotransformation in a series of alkoxy analogues were affected by the size of the alkoxy side chain, multiple dosing and pregnancy. There were increased recoveries of both the substrate and the conjugated derivative of PHA during gestation. The major metabolic routes observed were O-dealkylation, conjugation, and aliphatic hydroxylation of the propoxy side chain. There was some evidence of oxidative deamination. Pregnancy did not alter the profile of the major metabolites detected by GLC and NMR spectroscopy.

The dose- and time-related hepatotoxic effects of acetaminophen were investigated in rats using biochemical parameters as indices of hepatotoxicity supplemented by the histopathological examination of the livers. The acute or subacute (twice daily for 7 days) administration of 0.25 g/kg acetaminophen did not produce any noticeable hepatocellular damage. On the other hand, dose-dependent elevations in serum enzyme glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT) and sorbitol dehydrogenase (SDH) activities and hepatic triglyceride (TG) levels were observed following the administration of single doses of 0.5 and lg/kg acetaminophen. Maximal hepatic damage occurred 12-18 h after acute dosing, while the hepatic function returned to control levels by 48-72 h. In contrast with the acutely treated rats, the serum enzyme activities and the hepatic TG levels remained unchanged following 7-day treatment with 0.5 or 1 g/kg acetaminophen. Also, histopathologically the degree of acetaminophen-induced hepatic necrosis was found to be far less extensive in rats given 0.5 and 1 g/kg acetaminophen twice daily for up to one week, as compared with the animals sacrificed 18 h after administering single equivalent doses of this drug. The results suggest that the liver function is reversibly impaired following acetaminophen overdosage, and that the intensity of acetaminophen-induced hepatotoxicity becomes less severe after repeated exposure to this hepatotoxin.

The placental transfer, maternal tissue distribution and elimination of [14C]-nonoxynol-9 (25 mg/kg) were studied during the first 6 h in 15-day pregnant rats treated intravaginally. Blood concentrations of 14C reached a maximum of 2.0 +/- 0.06 micrograms/ml in 1 h, declining slowly in 3 h, and remaining steady thereafter. At 6 h, the highest levels of 14C were recorded in the maternal urinary bladder, followed by those in the liver, kidney, adrenal and thyroid. The maternal brain showed lowest uptake of 14C among all tissues examined. After 6 h, the 14C concentrations in the uterus or placenta were similar to that of maternal plasma, whereas the mean concentrations of 14C both in the amniotic fluid and fetus were approx. one-third of that of the maternal plasma. About 44% of the administered dose was absorbed from the vagina, and nearly 17% of the per vaginum applied radioactivity was recovered in the urine and feces over 6 h. The results show that nonoxynol-9 (N-9) is rapidly absorbed into the blood stream from the vagina of gravid rat and that the fetal uptake of 14C is much lower than that of the placenta.

The milk transfer, maternal-fetal distribution, and disposition of the antihypertensive/spermicidal agent propranolol were studied in pregnant and lactating rats. Single doses (10 mg/kg) of an aqueous solution of [14C]propranolol were administered either orally (po) or intravaginally (ivg) on gestational d 15, or on postpartum d 7-10. Upon ivg administration, [14C]propranolol was quickly transferred to systemic circulation and the mean blood [14C] concentrations were significantly greater during the first 0.25-2 h than in po dosed counterparts. About 98% of the ivg applied dose was absorbed after 6 h in gravid rats, and the combined 6-h excretions of radioactivity in the urine (ivg = 24.6%; po = 22.9%) and feces (ivg = 16.8%; po = 14.6%) were equivalent in both groups. At the end of 6 h, the levels of [14C] in the urinary bladder, adrenal, uterus, ovary, spleen, skeletal muscle, brain, heart, lung and fat were significantly higher in ivg treated rats than po dosed animals. Compared with the maternal plasma (ivg = 0.76; po = 0.88 microgram/ml), the mean concentrations of [14C] in the placentas were similar in both groups, while the amounts of [14C] were three to five times lower in the amniotic fluids and the fetuses of both po and ivg treated dams. In lactating rats, over 99% of the administered radioactivity was absorbed from the vagina within 6 h. The blood concentrations of [14C] were significantly elevated at 0.5 and 1 h in the per vaginam treated animals, and afterward the disappearance rate of [14C] followed a similar course in both groups. Following ivg application, the milk radioactivity peaked at 0.5 h and declined rapidly. However, the appearance of [14C] in milk was rather slow after oral dosing: the milk [14C] peaked between 2 and 3 h posttreatment and remained steady thereafter. The milk to blood (M/B) [14C] concentration ratios were markedly greater during 0.5 to 1 h in the ivg group than in their po dosed counterparts. At 6 h, the [14C] levels in the whole blood, plasma, milk, and mammary gland were virtually equivalent in the ivg and po treated females. Comparison of the areas under the milk [14C] concentration-time curves (AUCs) indicated that the milk availability of [14C] was about 31% more in dams dosed vaginally. These data suggest that route of administration alters the disposition and milk excretion of [14C]propranolol-derived radioactivity in pregnant and lactating rats.

Percutaneous absorption of the antimicrobial agent chlorhexidine (labelled with carbon-14) was studied in rats. Less than 5% of the topically applied chlorhexidine was absorbed during a 5-day period. Excretion of absorbed radioactivity occurred mainly in the faeces.

The effects of the spermicide benzalkonium chloride (BKC) were studied on the conceptus of rat. Single doses (0, 25, 50, 100 or 200 mg kg-1) of aqueous solutions of BKC were administered intravaginally (1 ml kg-1) on gestational day 1. The vulval metallic clips, used to prevent leakage of the solution, were removed 24 h post-treatment. Fetuses were obtained and examined for malformations on day 21 of gestation. slight to copious amounts of vaginal discharge and vaginitis were noticed in rats treated with the two largest doses of BKC. A dose-related increase in resorptions and fetal death, reduction in litter size and weight were observed in BKC-treated dams. The conceptus loss seemed to occur both before and after implantation. BKC did not cause any discernible visceral malformations, although minor sternal defects occurred in fetuses exposed to 100 and 200 mg kg-1 of the spermicide. These results suggest that single vaginal application of BKC is embryo- and fetocidal in the rat at a dose about 143 times higher than that recommended for controlling conception in women.

The pharmacokinetics of hexachlorophene (HCP) was studied in sexually mature virgin Wistar rats. [14C] HCP was injected either via the femoral vein, (ivn, 0.87 or 3.87 mg/kg in saline) or into the vaginal orifice (ivg, 0.87 mg/kg in corn oil). The disappearance of 14C from the blood after ivn administration followed the kinetics of a 2 compartment open model. The blood 14C profiles were superimposable, suggesting that the distribution and elimination rate constants for both doses were similar. After ivg application of [14C] HCP, 14C was detected in tail blood at 0.5 h, peaked between 2 and 4 h and disappeared slowly to 12 h but more rapidly thereafter. Less than 10% of the ivg dose of [14C] HCP remained in the vagina after 4 h. The cumulative recoveries of 14C in the faeces and urine 5 days after ivn administration were 85% and 4.6% of the dose, respectively. Comparable recoveries following ivg administration were 72% and 3.7%. The results suggest that HCP readily penetrates through the vaginal mucosa of the rat.