Search

Some plants used in traditional medicine to manage sickle cell disease have been validated pharmacologically to ascertain their anti-sickling properties. However, there is no global systematic review of the evidence in support of their use for sickle cell management. This research aimed to conduct a systematic review of the pharmacological evidence to highlight species, genera, and some phytochemicals which could be primed for novel anti-sickling medications. The Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines were used. Articles in English, published from 2000 to 2022 were included in the analysis. The literature search covered 411 publications of which 82 were found to be eligible. More than half (53.65%) of the articles were published from 2016 to 2022. Anti-sickling research from Africa accounted for 86.58% of the publications, with more than half coming from Nigeria, 12.20% from Asia and only 1.22% from Europe. The Fabaceae, Euphorbiaceae, and Annonaceae were the top three plant families whereas Zanthoxylum and Terminalia were the most reported genera. Carica papaya and Terminalia catappa were the most reported species. Sickling reversal (n = 33/82) and hemoglobin polymerization studies (n = 29/82) were the most reported assays. Benzoic acid derivatives, butyl stearate, ellagic acid derivatives, and some pentacyclic triterpenoids were the only plant derived compounds validated for anti-sickling activities. A total of 117 plant species with anti-sickling activities were documented. Studies on secondary metabolites with anti-sickling properties to serve as scaffolds for novel drug development for sickle cell management were limited. [ABSTRACT FROM AUTHOR]

The aqueous methanol extract (3:1, v/v) of the seeds of Cajanus cajan was investigated for antisickling properties. The extract possessed significant antisickling activity and was found to be concentration-dependent. The kinetics of reversal of presickled erythrocyte (HbSS) cells using the extract at 0.5 mg/mL, 1.0 mg/mL, 1.5 mg/mL, 2.0 mg/mL and 2.5 mg/mL showed first-order kinetics with rate constants of 5.833 x 10(-3) min(-1), 6.143 x 10(-3) min(-1), 5.957 x 10(-3) min(-1) 6.00 x 10(-3) min(-1) and 6.046 x 10(-3) min(-1), respectively, and with an average half-life 115.6 min. Phytochemical screening of the extract revealed the presence of free amino acids, phenolic compounds, tannins, globulins and saponins. These results show that the extract has potential use in the management of painful episodes experienced by sickle cell patients., (Copyright 2002 John Wiley & Sons, Ltd.)

Tissue disposition of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been shown to be dose-dependent in rats. However, no reported studies in mice have demonstrated dose- and time-dependent distribution of TCDD and the potential sensitivities of target tissues to enzyme induction. The objectives of this study were to determine in mice the effects of dose (0, 0.1, 1, or 10 micrograms [3H]TCDD/kg) and time (7, 14, 21, and 35 days posttreatment) on tissue distribution (18 tissues) and enzyme induction (CYP1A1 in liver, skin, and lung and CYP1A2 in liver). Distribution of TCDD-derived radioactivity in all tissues was dose- and time-dependent with nonlinear distribution. Liver-to-adipose tissue concentration ratios range from 0.6 to 3.1 (low to high dose at Day 7) demonstrating a dose-dependent shift in the disposition of TCDD. In contrast to liver, relative concentrations of percentage dose/g and percentage dose/total tissue decreased with increasing doses in all other tissues. At Day 7 and lowest dose, all tissues contained < 3% dose/g except for thyroid, adrenals, skin, liver, and adipose tissue which had 3, 6, 6, 15, and 24% dose/g, respectively. Induction of EROD activity, a marker for CYP1A1, was dose-dependent in liver, lung, and skin but did not parallel tissue concentrations of TCDD. At the highest dose, fold induction of EROD activity was two times greater in lung than liver, while the concentration in liver was 100 times greater than that in lung. Fold inductions of EROD activity in liver and skin were similar but the concentration was 20 times greater in liver than that in skin. Induction of hepatic acetanilide-4-hydroxylase (ACOH) activity, a CYP1A2 marker, was dose-dependent. Results of the present study demonstrated dose and time dependency in tissue distribution and induction of CYP1A1 and CYP1A2 as well as tissue sensitivities for enzyme induction in the female B6C3F1 mouse. These results provide important considerations for high- to low-dose extrapolations in risk assessments and use of sensitive markers of enzyme induction as surrogates for estimating exposure and in predicting risk.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has been reported to decrease host resistance to a variety of infectious agents when exposure occurs prior to infection. Resistance to viral infection has been observed at doses as low as 0.1 microgram TCDD/kg body wt, well below the thymolytic dose in mice. In the present study, female B6C3F1 mice were exposed to a single intraperitoneal injection of 0, 0.1, 1.0, 10.0, or 30.0 micrograms TCDD/kg 7 days prior to infection to determine the effects of TCDD exposure on resistance to the nematode parasite Trichinella spiralis. Exposure to 10 or 30 micrograms TCDD/kg delayed adult parasite elimination from the small intestine. Significantly more larvae were released by female parasites and greater numbers of encysted larvae were recovered from the muscle of mice exposed to TCDD. Proliferative responses of splenocytes and mesenteric lymph node cells stimulated with T. spiralis antigen were significantly suppressed at exposure levels of TCDD > or = 1.0 microgram/kg 7 days after infection and in splenocytes only at 14 days after infection, demonstrating the greater sensitivity of proliferative responses to TCDD exposure than actual host resistance to Ts infection. Suppressed proliferation was observed at doses which produced TCDD concentrations > or = 0.2 pmol/g of lymphoid tissue on Day 7 of infection. In addition, it was determined that infected mice had higher TCDD levels than noninfected mice given the same dose. These results suggest an interaction between TCDD exposure and infection, i.e., that exposure to TCDD altered the host response to infection, while infection delayed elimination of TCDD from the host.

A high pressure liquid chromatographic system (HPLC) has recently been developed for the simultaneous detection of malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON). We have examined the urinary excretion of these four lipid metabolites in the urine of rats following the acute oral administration of MDA (158 mg/kg body weight). During the first 12 h, increases in the urinary excretion of MDA and ACT of approximately 192- and 70-fold, respectively, were observed. The urinary excretion of both MDA and ACT decreased thereafter. An increase in FA excretion was observed only 12-24 h after MDA administration. A significant decrease in ACON relative to control values was observed 12-48 h after MDA treatment. Two new peaks were present in the HPLC chromatograms of urine samples 0-24 h after MDA administration. Both peaks were shown to be due to methyl ethyl ketone (MEK) which appears to be formed as a result of MDA metabolism. The results demonstrate that orally administered MDA is rapidly excreted in the urine, and alters the metabolism and excretion of other lipid metabolites.

Recent studies have shown that xenobiotics which induce oxidative stress result in an increased production and excretion of acetaldehyde (ACT), formaldehyde (FA), acetone (ACON) and malondialdehyde (MDA) in the urine of rats. We have therefore examined the effect of acute and chronic ethanol administration on the excretion of these four lipid metabolites in female Sprague-Dawley rats. Urine samples were collected over dry ice for 6 hr time periods. Aliquots of urine were derivatized with 2,4-dinitrophenylhydrazine HCl, and extracted with n-pentane. High pressure lipid chromatogrpahy (HPLC) was used to quantitate and the hydrazones of the four lipid metabolite products. Following a single, oral, acute dose of 5 g ethanol/kg, urinary excretion of ACT increased approximately 5.8-fold from 6 to 12 hr posttreatment, and decreased thereafter. FA excretion decreased by approximately 50% from 0 to 12 hr, returned to control values in the 18-24 hr urine samples, and was 1.3-fold greater than control values at 42-48 hr. ACON increased 3.1-fold over control values from 0 to 30 hr and remained elevated throughout the remaining 18 hr of the study. The excretion of MDA increased approximately 1.5-fold from 18 to 36 hr, then remained constant through the 48 hr time point. In a separate series of experiments, a chronic oral dose of 0.5 g ethanol/kg was administered to rats for 10 consecutive days and the urinary excretion of the lipid metabolites MDA, FA, ACT and ACON was examined for 11 days, beginning with the first day of ethanol administration.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of oral endrin administration to rats on the production of nitric oxide (NO) by peritoneal macrophages was investigated. Nitric oxide formation was measured as nitrite. Endrin (4.5 mg/kg) enhanced the secretion of NO by approx. 300%. The effect of endrin on NO formation was both dose- and time-dependent. Ellagic acid, which has been shown to be a potent antioxidant, inhibited the elevation of NO production induced by endrin. These results suggest that the toxicity of endrin may at least in part be due to the production of an oxidative stress.

Background: Sida linifolia L. is a weed ubiquitously found in Africa with several folkloric applications. Traditional healers in the Southeastern part of Nigeria employ the alcoholic concoction of S. linifolia leaves as antidepressants, anti-malaria, antihypertensive, anti-abortifacients, and for managing painful whitlow; however, these claims lack scientific validation. The present study was aimed to explore the phytochemical profile of the plant, S. linifolia with special emphasis to its antioxidant and inhibitory actions on enzymes linked to inflammation, diabetes, and neurological disorders. Phytochemical profiling and in vitro antioxidant and enzyme inhibition assays were employed to assess the pharmacological profile of S. linifolia ethanolic leaf fraction (SLELF). Results: Preliminary phytochemical screening of SLELF revealed appreciable amounts of total phenolics (91.64 ± 7.61 mg GAE/g), total tannins (62.44 ± 3.86 mg TAE/g), and total flavonoids (27.35 ± 1.48 mg QE/g) present in SLELF. Results of HPLC analysis of SLELF revealed rich composition in bioactive compounds such as ellagic acid, quercetin, ferulic acid, 3,4-dimethoxy benzoic acid, gallic acid, 4-methoxy cinnamic acid, sinapic acid, vanillic acid, and chlorogenic acid. Enzymatic antioxidants (catalase and superoxide dismutase), non-enzymatic antioxidants (reduced glutathione (GSH), Vit A, C, and E), elemental minerals (Cu, Mn, Zn, Cr, Fe, and Ca), and γ-aminobutyric acid (GABA) were present in SLELF in appreciable levels. At various concentrations (0.2–1.0 mg/ml), SLELF exhibited potent and concentration-dependent hydrogen peroxide (H2O2) and 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS) radical scavenging activities and exerted moderate inhibitory actions on enzymes associated with inflammation (cyclooxogenase-2 (COX-2) and lipoxygenases (LOXs), diabetes (α-amylase, α-glucosidase), and neurological disorders (butyrylcholinesterase (BChE) and γ-aminobutyric acid transaminase (GABA-T), compared to respective standards (ascorbic acid, acarbose, indomethacin, galanthamine, and vigabatrin). Perhaps, the observed potent pharmacological activities of SLELF could be anchored to its phytoconstituents. Furthermore, the slightly higher ranges of IC50 values (0.57–0.87 mg/ml) of SLELF compared to standards (0.44–0.68 mg/ml) suggest moderation in enzyme inhibition that may preclude adverse side effects. Conclusion: This study lends credence to the folklore claims of S. linifolia leaves and revealed its potential as possible source of bioactive compounds for medicinal and pharmaceutical exploration. [ABSTRACT FROM AUTHOR]

Herbalists in Nigeria use a variety of herbal remedies to treat various types of illness. Thirteen commonly used herbal plants in the Anambra State of Nigeria were identified and collected. Extracts were prepared and studied pharmacologically on various isolated and intact preparations. Toxicological and phytochemical studies were also conducted on most of these plants.

This study was undertaken to confirm or otherwise disprove the alleged effectiveness of Dioscorea dumetorum tuber in the traditional treatment of clinical diabetes mellitus. Hydroalcoholic extracts of the tuber were fractionated by precipitation or solvent partition and the various extracts or fractions subjected to phytochemical and pharmacological tests. Whereas the alkaloid-containing fraction was hyperglycaemic in fasting normal mice, the whole extract and the fractions containing steroidal derivatives evinced significant hypoglycaemic activities in fasting normal mice or rabbits and in fasting alloxan-diabetic rabbits. The hypoglycaemic action of the glycosidic portion in particular was prompt and potent, in normal as well as in severely alloxan-diabetic rabbits suggesting thereby the possibility of obtaining an agent that could act in conditions of even severe insulin lack.

Tetrodotoxin was used to investigate the site of action of 5-hydroxytryptamine on various longitudinal muscle preparations from the guinea-pig gastrointestinal tract. It was found that the contractile effect of 5-hydroxytryptamine on the oesophagus, the terminal ileum, the taenia caeci and the proximal colon was partly indirect through the activation of cholinergic fibres and partly direct on the smooth muscle. However on the stomach strip, the duodenum, the mid-intestine, the mid and terminal colons, the action is completely indirect through the stimulation of cholinergic nerves.

The methanol extract of the stem bark of Schumanniophyton magnificum and schumanniofoside, a chromone alkaloidal glycoside isolated from it, reduced the lethal effect of black cobra (Naja melanoleuca) venom in mice. This effect is greatest when the venom is mixed and incubated with the extract or schumanniofoside. It is thought that the mode of action is by oxidative inactivation of the venom.

The action of chloroquine on the histamine receptors was investigated on the guinea-pig isolated ileum. The log dose response curve to histamine in the presence of chloroquine (0.75 mug/ml) was to the right and parallel to that in the absence of the chloroquine. This concentration of chloroquine did not modify the contractions of the preparation to acetylcholine or to transmural stimulation. It had not effect on the contractions of the isolated vas deferens from the guinea-pig to either transmural stimulation or to hypogastric nerve stimulation. The pA2-pA10 value for chloroquine using histamine as the agonist was 0.87. It was concluded that chloroquine, in low concentration, is a specific antagonist of histamine, by probably a competitive mechanism.

Sickle cell disease is a genetic blood disorder that affects the shape and transportation of the red blood cells (RBCs) in blood vessels, leading to various clinical complications. Available medicines for treating the disease are insufficiently effective, toxic or expensive. Therefore, there has been a pressing need for effective and inexpensive therapeutic agents from indigenous medicinal plants. Petiveria alliacea, Canna indica and Pergularia daemia, respectively were evaluated for their cationic constituents as a measure for their antisickling activity in sickle cell anaemia disorder. The three medicinal plants were extracted separately with methanol solvent using maceration method for 72 hours. The extracts were concentrated using a rotary evaporator (Model RE, 200, USA). Phytochemical screenings were conducted using standard method, while other portions of the extract were subjected to dry ash digestion for determination of mineral elements by emission flame photometry (EFP) and atomic absorption spectrophotometry (AAS). Evaluation of the antisickling activity of the extracts was done using the sodium metabisulphite (SMBS) test. Eugenol, terpenoids and alkaloids were present in the three plant extracts, while K+ values recorded for Petiveria alliacea, Canna indica and Pergularia daemia were 54.30 mg kg-1, 180.10 mg kg-1 and 28.30 mg kg-1, respectively. Other mineral elements detected in the three plants were Cu2+, Zn2+, Fe2+ and Mg2+. The leaves extract of Canna indica and Pergularia daemia at high dose of 300 µg/mL caused significant reductions of sickle red blood cells from 15% to 6% and 15% to 1%, respectively at 90 minutes of the antisickling test. The research confirmed that extracts of both Canna indica and Pergularia daemia used in this study have significant antisickling properties in invitro studies than Petiveria alliacea. [ABSTRACT FROM AUTHOR]

Snakebite envenomations (SBEs) are a neglected medical condition of global importance that mainly affect the tropical and subtropical regions. Clinical manifestations include pain, edema, hemorrhage, tissue necrosis, and neurotoxic signs, and may evolve to functional loss of the affected limb, acute renal and/or respiratory failure, and even death. The standard treatment for snake envenomations is antivenom, which is produced from the hyperimmunization of animals with snake toxins. The inhibition of the effects of SBEs using natural or synthetic compounds has been suggested as a complementary treatment particularly before admission to hospital for antivenom treatment, since these alternative molecules are also able to inhibit toxins. Biodiversity-derived molecules, namely those extracted from medicinal plants, are promising sources of toxin inhibitors that can minimize the deleterious consequences of SBEs. In this review, we systematically synthesize the literature on plant metabolites that can be used as toxin-inhibiting agents, as well as present the potential mechanisms of action of molecules derived from natural sources. These findings aim to further our understanding of the potential of natural products and provide new lead compounds as auxiliary therapies for SBEs. [ABSTRACT FROM AUTHOR]

Persistent organic pollutants (POPs) are a diverse family of contaminants that show widespread global dispersion and bioaccumulation. Humans are continuously exposed to POPs through diet, air particles, and household and commercial products; POPs are consistently detected in human tissues, including the pancreas. Epidemiological studies show a modest but consistent correlation between exposure to POPs and increased diabetes risk. The goal of this review is to provide an overview of epidemiological evidence and an in-depth evaluation of the in vivo and in vitro evidence that POPs cause β-cell toxicity. We review evidence for six classes of POPs: dioxins, polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs), organophosphate pesticides (OPPs), flame retardants, and per- and polyfluoroalkyl substances (PFAS). The available data provide convincing evidence implicating POPs as a contributing factor driving impaired glucose homeostasis, β-cell dysfunction, and altered metabolic and oxidative stress pathways in islets. These findings emphasize the need to consider the endocrine pancreas in toxicity assessments. Our review also highlights significant gaps in the literature assessing islet-specific endpoints after both in vivo and in vitro POP exposure. In addition, most rodent studies do not consider the impact of biological sex or secondary metabolic stressors in mediating the effects of POPs on glucose homeostasis and b-cell function. We discuss key gaps and limitations that should be assessed in future studies. [ABSTRACT FROM AUTHOR]

Establishing factors that affect contaminants including potentially toxic metals in a freshwater and its surrounding soil is necessary to control the transfer of toxins into the food chain. We documented the seasonality in temperature, dissolved oxygen (DO), soil organic carbon (SOC), pH, and water color on the behavior of toxic metals in water and soil of Lake Nike. Slope and seasons statistically related significantly (p < 0.05) with DO and SOC. Only Ni was not statistically related significantly to pH, water color, and temperature of the water, while mercury and cadmium statistically related significantly to the soil pH. Temperature and pH were within the WHO safety limits which are 20–32 °C and 6.5–8.5, respectively, in both water and soil samples. Potentially toxic metals levels for lead (Pb) (0.47–2.10 mg/L), mercury (Hg) (0.57–2.01 mg/L), cadmium (Cd) (0.34–1.82 mg/L), and nickel (Ni) (0.56–2.09 mg/L) exceeded the 0.01, 0.001, 0.003, and 0.02 mg/L WHO safety limits, respectively, while Zinc (Zn) level which ranged from 0.24 to 2.51 mg/L was within the WHO limit (5 mg/L) and the standard organization of Nigeria (SON) limit (3.0 mg/L) in both seasons. From our study, Lake Nike could be relatively toxic, and unsafe for aquatic habitation and human consumption. [ABSTRACT FROM AUTHOR]

The WHO lists snakebite as a "neglected tropical disease". In tropical and subtropical areas, envenoming is an important public health issue. This review article describes the structure, function, chemical composition, natural inhibitors, and clinical applications of Elapids' Three Finger Toxins (3FTX) using scientific research data. The primary venomous substance belonging to Elapidae is 3FTX, that targets nAChR. Three parallel β-sheets combine to create 3FTX, which has four or five disulfide bonds. The three primary types of 3FTX are short-chain, long-chain, and nonconventional 3FTX. The functions of 3FTX depend on the specific toxin subtype and the target receptor or ion channel. The well-known effect of 3FTX is probably neurotoxicity because of the severe consequences of muscular paralysis and respiratory failure in snakebite victims. 3FTX have also been studied for their potential clinical applications. α-bungarotoxin has been used as a molecular probe to study the structure and function of nAChRs (Nicotinic Acetylcholine Receptors). Acid-sensing ion channel (ASIC) isoforms 1a and 1b are inhibited by Mambalgins, derived from Black mamba venom, which hinders their function and provide an analgesic effect. α- Cobra toxin is a neurotoxin purified from Chinese cobra (Naja atra) binds to nAChR at the neuronal junction and causes an analgesic effect for moderate to severe pain. Some of the plants and their compounds have been shown to inhibit the activity of 3FTX, and their mechanisms of action are discussed., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Spondias mombin Linn (Anacardiaceae) is a plant species found from southeastern Mexico to Peru and in the northern of Brazil. Its fruits are known as "cajá miúdo" or "cajá pequeno" in Brazil; in Central America, as "jobo"; as "hogplum" or "yellow mombin" in North America; and as "ciruella amarilla" in Mexico and Ecuador, among others. It is used by the local population to treat diseases due to its many biological properties, such as antiviral, anti-inflammatory, antioxidant, and antibacterial properties. This study was carried out using databases, indexed articles, theses, dissertations, and books. These surveys indicate important microscopic and macroscopic patterns of the species. Some studies also confirmed the popular use of S. mombin, showing in vitro and in vivo antioxidant properties and some activities, such as mosquito adulticidal, anti-inflammatory, antiviral, antibacterial, and anthelminthic activities. These properties are attributed to the abundant presence of phenolic compounds. Saponins, alkaloids, phenolic acids, tannins, and flavonoids are also found in its extracts. The results obtained in this study show several pharmacological applications that can lead to the development of new products and drugs based on the properties of S. mombin, which have already been reflected in field patents. [ABSTRACT FROM AUTHOR]

Background: Snake bites remain a major medical problem in West Africa, and hemorrhagic stroke following a snakebite has emerged as a rare secondary condition. The objective of this study was to determine the neurological complications following snake bite. Methods: This study included all the cases of hemorrhagic stroke following snake bite admitted in the neurology Department of Yalgado Ouedraogo University Teaching Hospital during the period from January 1st, 2018 to December 31st 2019. Results: Three cases of hemorrhagic stroke following snake bite were included in the study. The strokes occurred 4-15 days after the snakebite. Traditional treatment was applied in two cases. Complications were significant, including local manifestations and severe anemia in 2 patients who received blood transfusion. Snake anti-venom was applied. At admission, motor deficit, conscience disorders and fever were the most frequent complaints. Patients received repeated dose of snake anti-venom was applied, antitetanus prophylaxis and antibiotherapy during hospitalization. The majority of the patients had completely recovered. Conclusions: Hemorrhagic stroke following snake bites are rare in Burkina Faso. Clinical outcome of stroke was favorable after treatment by antivenom, anti-tetanus serum and antibiotics. [ABSTRACT FROM AUTHOR]

Context Human studies consistently show an association between exposure to persistent organic pollutants, including 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD, aka "dioxin"), and increased diabetes risk. We previously showed that a single high-dose TCDD exposure (20 µg/kg) decreased plasma insulin levels in male and female mice in vivo, but effects on glucose homeostasis were sex-dependent. Objective The current study assessed whether prolonged exposure to a physiologically relevant low-dose of TCDD impacts glucose homeostasis and/or the islet phenotype in a sex-dependent manner in chow-fed or high-fat diet (HFD)-fed mice. Methods Male and female mice were exposed to 20 ng/kg/d TCDD 2×/week for 12 weeks and simultaneously fed standard chow or a 45% HFD. Glucose homeostasis was assessed by glucose and insulin tolerance tests, and glucose-induced plasma insulin levels were measured in vivo. Histological analysis was performed on pancreas from male and female mice, and islets were isolated from females for TempO-Seq transcriptomic analysis. Results Low-dose TCDD exposure did not lead to adverse metabolic consequences in chow-fed male or female mice, or in HFD-fed males. However, TCDD accelerated the onset of HFD-induced hyperglycemia and impaired glucose-induced plasma insulin levels in females. TCDD caused a modest increase in islet area in males but reduced the percent beta cell area within islets in females. TempO-Seq analysis suggested abnormal changes to endocrine and metabolic pathways in female TCDDHFD islets. Conclusion Our data suggest that prolonged low-dose TCDD exposure has minimal effects on glucose homeostasis and islet morphology in chow-fed male and female mice but promotes maladaptive metabolic responses in HFD-fed females. [ABSTRACT FROM AUTHOR]

Diabetes prevalence is increasing worldwide, and epidemiological studies report an association between diabetes incidence and environmental pollutant exposure. There are >84,000 chemicals in commerce, many of which are released into the environment without a clear understanding of potential adverse health consequences. While in vivo rodent studies remain an important tool for testing chemical toxicity systemically, we urgently need high-throughput screening platforms in biologically relevant models to efficiently prioritize chemicals for in depth toxicity analysis. Given the increasing global burden of obesity and diabetes, identifying chemicals that disrupt metabolism should be a high priority. Pancreatic endocrine cells are key regulators of systemic metabolism, yet often overlooked as a target tissue in toxicology studies. Immortalized β-cell lines and primary human, porcine, and rodent islets are widely used for studying the endocrine pancreas in vitro , but each have important limitations in terms of scalability, lifespan, and/or biological relevance. Human pluripotent stem cell (hPSC) culture is a powerful tool for in vitro toxicity testing that addresses many of the limitations with other β-cell models. Current in vitro differentiation protocols can efficiently generate glucose-responsive insulin-secreting β-like cells that are not fully mature, but still valuable for high-throughput toxicity screening in vitro. Furthermore, hPSCs can be applied as a model of developing pancreatic endocrine cells to screen for chemicals that influence endocrine cell formation during critical windows of differentiation. Given their versatility, we recommend using hPSCs to identify potential β-cell toxins, which can then be prioritized as chemicals of concern for metabolic disruption. [ABSTRACT FROM AUTHOR]

Schumanniophyton magnificum Harms (Rubiaceae) is used traditionally in Nigeria for the treatment of snake bites. Snake venom contains phospholipase A2 (PLA2) which plays a key role in causing inflammation and pain. To assess the anti-inflammatory effect of the methanol extract of Schumanniophyton magnificum (MESM) leaves through the inhibition of PLA2 and investigate the compounds responsible for the effect. PLA2-inhibitory activity of MESM was assessed at concentrations of 0.1–0.8 mg/mL using human red blood cells as substrate. Prednisolone was used as the standard control. MESM was subsequently partitioned using n-hexane, dichloromethane, ethyl acetate and aqueous-methanol (90:10 v/v), after which PLA2-inhibitory activity of the partitions was determined. The best partition was subjected to chromatographic techniques and the fractions obtained were assessed for PLA2 inhibition at 0.4 mg/mL. Compounds in the most active fraction were determined using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GC-MS). MESM significantly inhibited PLA2 activity at 0.8 mg/mL (44.253%) compared to prednisolone (35.207%). n-Hexane partition (SMP1) proved more active with inhibition of 55.870% observed at 0.1 mg/mL. Fraction 1 (SMF1) showed the highest PLA2-inhibitory activity of 58.117%. FTIR studies revealed the presence of some functional groups in SMF1, and GC-MS confirmed the presence of 9 compounds which are first reported in this plant. Hexadecanoic acid, ethyl ester was identified as the major compound (24.906%). The PLA2-inhibitory activity of MESM suggests that its compounds may be explored further in monitoring anti-inflammatory genes affected by the venoms. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Pharmaceutical Sciences is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Gynecological Endocrinology is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Aims/hypothesis: Exposure to environmental pollution has been consistently linked to diabetes incidence in humans, but the potential causative mechanisms remain unclear. Given the critical role of regulated insulin secretion in maintaining glucose homeostasis, environmental chemicals that reach the endocrine pancreas and cause beta cell injury are of particular concern. We propose that cytochrome P450 (CYP) enzymes, which are involved in metabolising xenobiotics, could serve as a useful biomarker for direct exposure of islets to pollutants. Moreover, functional CYP enzymes in islets could also impact beta cell physiology. The aim of this study was to determine whether CYP1A enzymes are activated in islets following direct or systemic exposure to environmental pollutants. Methods: Immortalised liver (HepG2) and rodent pancreatic endocrine cell lines (MIN6, βTC-6, INS1, α-TC1, α-TC3), as well as human islets, were treated in vitro with known CYP1A inducers 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (3-MC). In addition, mice were injected with either a single high dose of TCDD or multiple low doses of TCDD in vivo, and islets were isolated 1, 7 or 14 days later. Results: CYP1A enzymes were not activated in any of the immortalised beta or alpha cell lines tested. However, both 3-MC and TCDD potently induced CYP1A1 gene expression and modestly increased CYP1A1 enzyme activity in human islets after 48 h. The induction of CYP1A1 in human islets by TCDD was prevented by cotreatment with a cytokine mixture. After a systemic single high-dose TCDD injection, CYP1A1 enzyme activity was induced in mouse islets ~2-fold, ~40-fold and ~80-fold compared with controls after 1, 7 and 14 days, respectively, in vivo. Multiple low-dose TCDD exposure in vivo also caused significant upregulation of Cyp1a1 in mouse islets. Direct TCDD exposure to human and mouse islets in vitro resulted in suppressed glucose-induced insulin secretion. A single high-dose TCDD injection resulted in lower plasma insulin levels, as well as a pronounced increase in beta cell death. Conclusions/interpretation: Transient exposure to TCDD results in long-term upregulation of CYP1A1 enzyme activity in islets. This provides evidence for direct exposure of islets to lipophilic pollutants in vivo and may have implications for islet physiology. [ABSTRACT FROM AUTHOR]

Heavy metals are leading causes of environmental contamination and arsenic (As) is currently one of the most important metal contaminants particularly in the developing countries such as Nigeria. The effects of chromatographic fractions of Spondias mombin L. (SM) leaves on sodium arsenite-induced toxicities in male Wistar rats were evaluated. Thirty-five male rats allotted equally into seven groups (A - G): Groups A and B were treated with 0.1 mL 1% dimethylsulphoxide (DMSO) and distilled water respectively, Group C: sodium arsenite (SA) 2.5 mg/kg, Group D: 100 mg/kg ethyl acetate fraction of SM, Group E: 100 mg/kg ethyl acetate fraction of SM and 2.5 mg/kg SA, Group F: 100 mg/kg methanol fraction of SM and SA, Group G: 100 mg/kg methanol fraction. SM was administered orally for 14 days, while SA was administered as a single oral dose on the 14th day of treatment with SM. Blood was taken 24 hours after SA administration and the animals were sacrificed. Phytochemical, haematological, biochemical, histopathological analyses and micronucleated polychromatic erythrocytes (MnPCEs) induction in the bone marrow cells were evaluated at the termination of the experiment. Phytochemical screening revealed alkaloids, tannins, phenols and flavonoids in all the fractions. Ethyl acetate and methanol fractions contained cardiac glycosides and carbohydrates whereas only hexane and ethyl acetate fractions contained steroids. Results showed normocytic hypochromic anaemia, genotoxicity, kidney and perilobular hepatic damage in the group that received SA alone, which were significantly (p<0.05) ameliorated by the fractionated extracts. The PCV, Hb, MCV and MCH values for group G, which was treated with methanol fraction alone were significantly higher (p<0.05) while the differential Lymphocytes and Neutrophils counts were significantly increased (p<0.05) in group D. The changes in the mean values of AST, ALP and BUN for Groups D and G were significantly lower (p<0.05) when compared with group B. In conclusion, the methanol and ethyl acetate fractions of S. mombin, exhibited hepatoprotective, nephroprotective and genoprotective properties against sodium arsenite-induced toxicity in Wistar rats. [ABSTRACT FROM AUTHOR]

Purpose: Parquetina nigrescens (Pn) extract was evaluated for safety and antidiarrheal activity, formulated into stable suspensions, and characterized. Methods: Acute toxicity of the extract based on Organization for Economic Cooperation and Development-423 guidelines was performed. The antidiarrheal effects of the extract on castor oil-induced diarrhea in four groups of Wistar rats were determined. The first and second groups received 5 and 200 mg/kg body weight (bw) of the extract, while the third and fourth groups received normal saline (5 mg/kg bw) and loperamide (5 mg/kg bw) as negative and positive controls, respectively. Pn extract was used at 1.25% w/v to formulate structured vehicle (carboxylmethylcellulose, polyvinylpyrrolidone and tragacanth) suspensions. The suspensions were tested for pharmacological activity and characterized. Results: Acute toxicity gave a lethal dose 50 (LD50) that is greater than 300 and less than 2,000 mg/kg bw. A reduction in intestinal transit by 0.14 and 0.15% at 5 and 200 mg/kg of the extract was achieved as compared to an inhibition of 0.12% by 5 mg/kg loperamide. There was a dose-dependent decrease in the frequency of watery stool passed in castor oil-induced rats by 35.29% and 64.70% at 5 and 200 mg/kg, respectively. All the suspensions inhibited diarrhea, exhibiting a dose-dependent pattern and remained stable after 4 weeks. Their pH values ranged from 4.60±2.73 to 4.73±1.91, while viscosity ranged from 3.50±1.23 to 6.75±1.24 Pas at 60 rpm. Conclusion: The results suggest that Pn possesses significant antidiarrheal activity. Suspensions of Pn were successfully formulated in structured vehicles and were effective in the control of diarrhea in Wistar rats. [ABSTRACT FROM AUTHOR]

Onchocerciasis is a filarial vector borne disease which affects several million people mostly in Africa. The therapeutic approach of its control was based on a succession of drugs which always showed limits. The last one: ivermectin is not the least. It was shown to be only microfilaricidal and induced resistance to the human parasite Onchocerca volvulus. The approach using medicinal plants used in traditional medicine is a possible alternative method to cure onchocerciasis. Onchocerca ochengi and Onchocerca gutturosa are the parasite models used to assess anthelmintic activity of potentially anthelmintic plants. Numerous studies assessed the in vitro and/or in vivo anthelmintic activity of medicinal plants. Online electronic databases were consulted to gather publications on in vitro and in vivo studies of anti-Onchocerca activity of plants from 1990 to 2017. Globally, 13 plant families were investigated for anti-Onchocerca activity in 13 studies. The most active species were Anacardium occidentale, Euphorbia hirta and Acacia nilotica each with an LC50 value of 2.76, 6.25 and 1.2 μg/mL, respectively. Polycarpol, voacamine, voacangine, ellagic acid, gallic acid, gentisic acid, 3-O-acetyl aleuritolic acid and (−)-epigallocatechin 3-O-gallate were the isolated plant compounds with anti-Onchocerca activity. Most of the assessed extract/compounds showed a good safety after in vivo acute toxicity assays and/or in vitro cytotoxicity test. The exception was the ethanol extract of Trichilia emetica, which killed completely and drastically mice at a dose of 3000 mg/kg. Several plant groups of compounds were shown active against Onchocerca sp. such as tannins, alkaloids, triterpenoids and essential oils. Nevertheless, none of the active compounds was subjected to clinical trial, to assessment of its diffusibility through nodular wall or its capability to induce genetic resistance of Onchocerca sp. [ABSTRACT FROM AUTHOR]

Squamous cell carcinoma of oral cavity is of malignant tumors, which causes cancerous complications. DNA damage, mainly because of products of oxidative stress like reactive oxygen species, is a frequent mutagenic that triggers carcinoma. Smoking increases the probability of cancer incidence. Saliva is the first biological medium to interact with external compounds, especially smoking substances. The present study overviews the salivary level of some remarkable compounds in relation with smoking and squamous cell carcinoma. To collect data, English literature was searched in databases including PubMed, ScienceDirect and Google Scholar. The keywords used for search were as follows: ‘Carcinoma, Squamous Cell', ‘Smoking', ‘Saliva’, and ‘Biomarkers‘. The inclusion criteria were the presence of salivary chemical factors in relation with oral cancer and influence by smoking. Out of 239 found articles, only 56 were selected. Our results demonstrated the potential role of salivary biochemistry to predict and/or treat complications with cancer in both smoker and non-smoker individuals. Changes in concentrations of salivary chemicals including antioxidants, total antioxidant, glutathione and uric acid, epithelial growth factor, cytokine biomarkers, superoxide dismutase activity, and transcriptome were related to squamous cell carcinoma and could be used as potential biomarkers for cancer prognosis; moreover, enhancement of antioxidant level might be a potential treatment. [ABSTRACT FROM AUTHOR]

Rhizobacterial production of plant hormones, ACC deaminase, fixation of nitrogen, solubilization of phosphate and antimicrobial metabolites play very important role in the health and growth of plants. Hence exploration of plant probiotic prospectives of promising rhizobacterial isolates from biodiversity rich areas can have enormous applications to engineer both the biomass and active ingredients of plants. In the present study, rhizospheric Proteus spp. R6 and R60 isolated from Pseudarthria viscida and Glycosmis arborea were analyzed for tuber and diosgenin enhancement effects in Dioscorea nipponica under field conditions for 1 year. Among the two Proteus spp. selected, both were positive for ACC deaminase, siderophore, nitrogen fixation, IAA and ammonia production. However, the isolate R6 was found to have additional phosphate solubilizing activity. Quantitative analysis of IAA by HPTLC showed its maximum production by Proteus sp. R60 (714.47 ± 8.7 µg/mL) followed by Proteus sp. R6 (588.06 ± 7.0 µg/mL). The tubers formed from the Proteus sp. R6 treated samples were identified to have significant enhancement in size, root number and diosgenin content when compared to control. Interestingly, HPLC analysis has confirmed twofold higher diosgenin content in Proteus sp. R6 treated samples than control during 1 year period of its field growth. The obtained results are of great importance as it involved the utilization of rhizospheric bacteria to improve tuber size which suggests its potential use in developing cost-effective, eco-friendly and multifunctional biofertilizer. [ABSTRACT FROM AUTHOR]

Background: The use of the modified-prescription event monitoring technique has facilitated the understanding and reporting of pharmacovigilance (PV). However, in Nigeria, PV activities are largely misunderstood. Furthermore, there is a dearth of information on the knowledge and perceptions of pharmacy students on PV activities in relation to demographics. This study investigated and assessed the knowledge and perceptions of pharmacy students about pharmacovigilance as well as the demographic factors that are related to pharmacovigilance activities. Methods: A cross-sectional survey was conducted among final year pharmacy students in three universities in months of January and February, 2016 with permission from the institutions and with written consents from 342 respondents. Pre-tested questionnaire was used to elicit information on the study objectives. Data were analysed using appropriate descriptive and inferential statistical techniques. Results: The study revealed that the mean score on knowledge of pharmacy students on pharmacovigilance activities was 4.3 ± 0.18 which was significant according to gender (P < 0.001), students' university (P < 0.001), and previous exposure to PV subjects (P < 0.001). Sixty-four percent of the students had positive perceptions about PV activities which was significant at P < 0.00 according to gender and their various universities. Less than half of the respondents 165 (48.2%) were able to correctly name the organisation that collates and document ADR reports in Nigeria. Only 21 (6.1%) of the respondents gave the correct answer to whether or not all possible ADRs of a drug can be determined during clinical trials or during pre-marketing phase of drug assessment. About 204 (59.7%) of the respondents erroneously believed that adverse reactions caused by cosmetics should not be reported. Conclusions: Respondents have inadequate knowledge of PV activities. Therefore, pharmacy student educators should enhance students' knowledge about PV through training, during clerkship, and lay more emphasis on relevant PV courses in the Pharmacy Curriculum. [ABSTRACT FROM AUTHOR]

I would certainly never have predicted that I would become the director of the National Institute of Environmental Health Sciences (NIEHS) and the National Toxicology Program (NTP) when I was a Jewish girl growing up in Teaneck, New Jersey. My family stressed the importance of education. Yet for a girl there were many not-so-subtle suggestions that the appropriate careers were in teaching or nursing, and the most important thing was to be a wife and mother. Well, I can't disagree with the latter, although I would have to add grandmother to that list of achievements. My parents were both college graduates, but my mom only taught high school English for one year before leaving the field to start our family. My dad returned from World War II and joined his brother in accounting. After my first sister was born, my father joined my mother's family jewelry business and helped to open a second retail store. My mother helped my dad out during the busy times-Christmas and wedding season-but otherwise focused on our growing family of three girls and one boy. This became increasingly challenging when it became clear that my little brother was severely retarded and would require extra care. [ABSTRACT FROM AUTHOR]

As part of an ongoing study of Anacardiaceae subfamily Spondioideae, the ten native and one introduced species of Spondias in the Neotropics are revised. The genus is circumscribed. Three new species, S. admirabilis, S. expeditionaria, and S. globosa, are described and illustrated; a key to the taxa found in the Neotropics and distribution maps are provided. The Paleotropical species and allied genera are reviewed. Diagnostic character sets include leaf architecture, habit, flower morphology, and gross fruit morphology. Notes on the ecology and economic botany of the species are provided. [ABSTRACT FROM AUTHOR]

The effect of two different contamination levels of T-2 toxin (1.5 or 3.4mg/kg feed) was investigated in a 28-days feeding trial on body weight, relative weight of liver and spleen, and some lipid peroxidation and glutathione redox parameters of 14-days old broiler chicken. The results showed that T-2 toxin decreased significantly the body weight at both contamination levels and showed a dose-dependent tendency. Relative weight of liver increased till the end of the trial, while relative weight of spleen was lower at both samplings at lower level of T-2 toxin exposure. Initial phase of lipid peroxidation (conjugated dienes and trienes) was not detected in the liver, but as product of later phase, thiobarbituric acid reactive substances increased significantly, except in the liver. Glutathione content on day 14 was higher in liver homogenate as compared to the control at the lower T-2 toxin contamination level. On day 28 it was higher in blood plasma at the higher and in liver homogenate at both levels of T-2 contamination. Glutathione peroxidase activity on day 14 was significantly higher in liver and spleen homogenates as compared to the control at the lower level of T-2 toxin contamination. On day 28, significantly higher activity was found at both T-2 toxin contamination levels in liver homogenate, and at the lower contamination level in spleen homogenate as compared to the control. The results revealed that T-2 toxin exposure initiates lipid peroxidation and activates the glutathione redox system as well, but the changes were irrespective of the dose- and partly duration of the exposure. [ABSTRACT FROM AUTHOR]

The clinicopathological parameters of 25 Yankasa sheep of both sexes weighing between 10 and 23 kg, aged 6-12 months, were evaluated under experimental conditions following infection with Haemonchus contortus. Clinical parameters (temperature, respiratory rate, pulse rate, faecal egg count and body weight) were evaluated before and after infection, as well as before and after treatment. Also, gross and histopathological changes were determined. Changes in body weight, temperature, pulse rate and respiratory rate of the experimental animals were not statistically significant ( P > 0.05), while the changes observed in egg per gram (EPG) count were statistically significant ( P < 0.05). Clinical signs observed include the following: weakness, dullness, diarrhoea, emaciation and reduced feed intake prior to treatment. However, there was amelioration of clinical signs and reversion of clinical parameters to near pre-infection values on day 42 post-infection among the albendazole and extract-treated groups following treatment on day 21 post-infection. At post-mortem, carcasses of animals in groups D and C were pale with ulcers on the abomasal mucuosa. The abomasum and the lung showed multifocal areas of congestion. Histopathologically, the liver showed congestion of the central vein with the presence of eosinophil in the central veins and the sinusoids; there were multifocal eosinophilic and lymphocytic infiltrations in the submucosa and lamina propria with vacuolation of the abomasal glands. Changes similar to those seen in haemonchosis under natural conditions were also observed. Significant P < 0.05 decrease was observed in EPG following treatment with the extract. P < 0.05 was considered significant throughout the study. [ABSTRACT FROM AUTHOR]