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AIM: To assess the hyperglycemia-induced microscopic changes in the posterior pituitary of streptozotocin (STZ) - induced diabetic adult albino rats. MATERIAL AND METHODS: After clearance from the Institutional Animal Ethical Committee, 36 animals were divided into six groups having six rats each: control, two weeks, one month, two months, four months and six months. Diabetes was induced with a single dose of streptozotocin administered through intraperitoneal route (60 mg/kg). Body weight and blood sugar were monitored at the biweekly interval. At the end of each experimental period, animals were euthanized by deep ether anesthesia and blood samples were collected by direct puncture of heart for biochemical analysis. Tissues were fixed in Karnovsky fixative and processed for paraffin sectioning. Routine and special stained sections were studied under the light microscope and relevant findings were recorded. RESULTS: Data obtained from biochemical analyses and histomorphometry along with the histopathological features revealed that with increasing duration of hyperglycemia was associated with increased serum creatinine and reduction in serum total protein; increased mean percentage of darkly stained large sized pituicytes and notable thickening of perisinusoidal collagen. CONCLUSION: It is therefore concluded that long-standing hyperglycemia which is associated with increased occurrence of predominantly large and darkly stained pituicytes and remarkably increased deposition of perisinusoidal collagen appear to be the important contributing factors somehow responsible for the derangement of the function of the posterior pituitary in chronic diabetes.

Although topical application of nucleic acids offers many potential therapeutic advantages for suppressing genes in the skin, topical delivery of siRNA for skin cancer treatment remains in its infancy. In the present study, the anticancer efficacy of a dendrosome-based formulation of polo-like kinase enzyme (PLK-1) specific siRNA was evaluated against DMBA induced skin papillomas in Swiss albino mice. The efficacy of the dendrosome based siRNA nano-formulation was evaluated on the basis of the effect on total numbers and sizes of tumor papillomas and the expression of apoptotic factors. The nano-formulation was successful in reducing the cumulative numbers as well as sizes of tumor nodules and causing significant apoptosis of skin tumor cells which led to better survival of the treated animals. The results indicate that dendrosomes are promising nanocarriers for the development of topical gene silencing approaches to treat skin tumors.

Our objective is to study the nephroprotective activity and antioxidant potential of Bauhinia purpurea unripe pods and bark against cisplatin-induced nephrotoxicity. Healthy adult albino rats of either sex (150-200 g) were randomly divided into six groups of six animals each Group I (vehicle control) and Group II (negative control). Group III (BBE200) and Group IV (BBE400) were administered the ethanolic extract of Bauhinia purpurea bark in doses of 200 and 400 mg/kg/day p.o., respectively, and Group V (BPE200) and Group VI (BPE400) were administered the ethanolic extract of Bauhinia purpurea unripe pods at doses of 200 and 400 mg/kg/day p.o., respectively. All the treatments were given for nine days. Cisplatin in a single dose of 6 mg/kg i.p. was given on the 4 th day to all groups, except the vehicle control group. On the 10 th day, blood and urine were collected for biochemical tests and the rats were sacrificed. The kidney was removed for histology and lipid peroxidation-antioxidant test. Cisplatin caused nephrotoxicity as evidenced by elevated blood urea, serum creatinine and urine glucose, and there was decreased creatinine clearance in Group II as compared with Group I. Administration of BBE and BPE at doses of 200 and 400 mg/kg in Group III and Group VI caused a dose-dependant reduction in the rise of blood urea, serum creatinine and urine glucose, and there was a dose-dependant increase in creatinine clearance compared with Group II. There was increased catalase and glutathione and decreased malondialdehyde levels in Group II, while BBE 400 (Group IV) and BPE 400 (Group VI) treatments significantly reversed the changes toward normal values. Histological examination of the kidney revealed protection in Group IV and Group VI compared with Group II. The ethanolic extract of Bauhinia purpurea unripe pods and bark has a nephroprotective activity against cisplatin-induced nephrotoxicity in rats.

Cis-Diamminedichloroplatinum II- (CP-) induced neurotoxicity is one of the least explored aspects of this drug. Dorsal root ganglia (DRG) cells are considered as the primary target, and their damage plays a vital role in pathogenesis and etiology of CP-induced neurotoxicity. The present study is aimed at confirming if riboflavin (RF) has any protective role in shielding the DRG from CP-induced toxicity. After conducting the established treatment strategy on mice under photoillumination, it was observed that, despite the fact that RF alone is partially toxic, its combination with CP significantly ameliorated the drug-induced damage in DRG cells as evidenced by histological analysis. In addition, it was interesting to observe that the combination group (RF + CP) was able to induce apoptosis in the target cells up to a significant extent which is considered as the most preferred way of countering cancer cells. Therefore, RF can act as an effective adjuvant compound in CP-based chemoradiotherapy to improve clinical outcomes in the contemporary anticancer treatment regimes.

Background: Non-steroidal anti-inflammatory drugs are very commonly used as an analgesic, antipyretic, anti-inflammatory, and antiplatelet agent. They have significant adverse effect on liver and kidney besides damaging stomach. Their effect on liver and kidney are of serious concern. Hence, we have decided to study the preventive effect of Nigella sativa against paracetamol induced hepatic and renal damages. Methods: Ethanolic and aqueous extracts of N. sativa were prepared with the help of Soxhlet’s apparatus. Totally, 36 wistar albino rats (150-200 g) of either sex were divided into six groups of six each. Group I was administered with distilled water, Group II-VI were treated with paracetamol 750 mg/kg i.p. Group III-VI were test groups also treated with N. sativa aqueous extract (200 and 400 mg/kg p.o) and ethanolic extract (200 and 400 mg/kg p.o), respectively. The treatment was given daily for 7 days and on 8th all the rats were sacrificed and the blood was analyzed for hepatic and renal function tests and tissue was preserved for histopathological examination. Results: Paracetamol administration caused a marked hepatic and renal damage, which is evidenced by the increase in liver and renal function test parameters in the negative control group. N.sativa extracts prevented this damage. The protective was seen maximum in ethanolic extract followed by the aqueous extract in dose-dependent manner. Conclusion: Ethanolic extract showed significant protection against paracetamol-induced and renal damage.

Objectives : One of the common clinical observations regarding long-standing hyperglycemia is autonomic neuropathy, probably due to its unfavorable destructive effects on the neurons of the autonomic ganglia. Accordingly, the current study was aimed to analyze the effect of experimental hyperglycemia on parasympathetic pterygopalatine ganglion (PtG) and sympathetic coeliac ganglion (ClG) of albino rats. Methods: Thirty-six albino rats were divided into six groups (n=6, each) and were designated as control, two weeks, one month, two months, four months and six months groups. Diabetes was induced with a single dose of streptozotocin (STZ, 60 mg/kg, i.p.). Body weight and blood sugar were monitored at biweekly intervals. At the end of each experimental period, animals were euthanized by deep ether anesthesia and blood samples were collected by direct puncture of heart for biochemical analysis. Animals were perfused with Karnovsky fixative. After 48 hours, tissue samples were collected and processed for light microscopy. Results : Biochemical analysis of serum revealed increased serum creatinine and reduced serum total protein. Histopathology and histomorphometry of ganglia revealed that the progressively increasing duration of hyperglycemia was associated with decreased proportion of small-sized neurons, increased proportion of large-sized neurons, dark and dead neurons, and thickening of capsular and endoneurial collagen. Conclusion: The association of the long-standing hyperglycemia with increased neuronal death, altered proportion of neurons and deposition of collagen fibers in autonomic ganglia appear to be important contributing factors likely to be responsible for diabetic autonomic neuropathy.

Cisplatin (CP) is an effective anti-cancer drug which causes remarkable toxicity to the kidney, particularly to proximal tubules, by generating reactive oxygen species. Nigella sativa (NS), commonly known as "black cumin" reduces the progression of various kidney disorders. Thymoquinone (TQ), the major bioactive constituent of NS seeds, has been credited for various pharmacological effects of NS. Since, a typical clinical CP dosing regimen involves CP administration in multiple cycles over a long time duration, hence the present study aimed to evaluate the renoprotective efficacy of NS oil and TQ against multiple dose CP treatment induced deleterious biochemical and histological alterations in rat kidney. Adult male Wistar rats were divided into six groups viz. control, CP, CPNSO, CPTQ, NSO and TQ. Animals in CPNSO and CPTQ groups were pre-administered NSO (2ml/kg bwt, orally) and TQ (1.5mg/kg bwt, orally) respectively for 14 days and were then treated with CP (3mg/kg bwt, i.p), every fourth day for 20 days while still receiving NSO/TQ. NSO and TQ administration, prior to and along with CP treatment, attenuated CP induced renal functional impairment as evident by significantly restored serum creatinine and blood urea nitrogen levels. CP treatment alone led to significant decline in the specific activities of brush border membrane (BBM) marker enzymes viz. ALP (-46.64%), GGTase (-50.24%) and LAP (-42.15%), while NSO or TQ administration to CP treated rats significantly prevented the decline in the activities of these enzymes in isolated BBM vesicles (BBMVs) as well as in the homogenates of renal cortex and medulla. Furthermore, both NSO and TQ administration also mitigated the CP induced perturbations in renal metabolic and redox status. Histological studies supported these biochemical results showing significant attenuation of CP induced kidney damage in CPNSO and CPTQ cotreated groups. Thus, NSO and TQ have excellent scope for use as functional food or combinatorial nutraceuticals in CP chemotherapy to ameliorate the accompanying nephropathy in long term cancer chemotherapy.

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). MRSA is an important pathogen in the healthcare sector that has neither been eliminated from the hospital nor community environment. In humans, S. aureus causes superficial lesions in the skin and localized abscesses, pyogenic meningitis/encephalitis, osteomyelitis, septic arthritis, invasive endocarditis, pneumonia, urinary tract infections and septicemia. Investigations focused in the search of other alternatives for the treatment of MRSA infections are in progress. Among the range of compounds whose bactericidal activity is being investigated, ZnO nanoparticles (ZnO-NPs) appears most promising new unconventional antibacterial agent that could be helpful to confront this and other drug-resistant bacteria. The aim of present study is to investigate the antibacterial potential of ZnO-NPs against Staphylococcus species isolated from the pus and wounds swab from the patients with skin and soft tissue infections in a tertiary care hospital of north India. ZnO-NPs (≈19.82 nm) synthesized by sol-gel process were characterized using scanning electron microscopy, X-ray diffraction , and Atomic force microscopy. The antibacterial potential was assessed using time-dependent growth inhibition assay, well diffusion test, MIC and MBC test and colony forming units methods. ZnO-NPs inhibited bacterial growth of methicillin-sensitive S. aureus (MSSA), MRSA and methicillin-resistant S. epidermidis (MRSE) strains and were effective bactericidal agents that were not affected by drug-resistant mechanisms of MRSA and MRSE.

Anticancer drugs are generally plagued by toxic manifestations at doses necessary for control of various forms of cancer. Incorporating such drugs into liposomes not only reduces toxicity but also enhances the therapeutic index. Some antioxidants and potent immunomodulators have also been shown to impart significant antitumor activity presumably by nonspecific activation of the host immune system. In the present study, we evaluated augmentation of the antitumor activity of etoposide (ETP) by the immunomodulator tuftsin in Swiss albino mice with fibrosarcoma. The efficacies of the free form of ETP, liposomized ETP (Lip-ETP), and tuftsin-bearing liposomized ETP (Tuft-Lip-ETP) formulations were evaluated on the basis of tumor regression, effect on expression level of p53wt and p53mut, and survival of the treated animals. Tuft-Lip-ETP, when administered at a dosage of 10 mg/kg body weight/day for five days, significantly reduced tumor volume, delayed tumor growth, and also up-regulated the expression of p53wt. In contrast, although Lip-ETP delayed tumor growth, it did not decrease tumor size. The results of the present study suggest that tuftsin incorporation in drug-loaded liposomes is a promising treatment strategy for various forms of cancers, including fibrosarcoma.

In diabetes the structural and functional recovery of skeletal muscle is impaired due to persistent hyperglycemia-induced oxidative stress. Vitamin E is known to be essential antioxidant for maintains the skeletal muscle homeostasis thus preventing oxidative damages. This study is designed to explore the effect of d-α-tocopherol and d-δ-tocotrienol rich fraction (d-δ-TRF) on crushed muscle regeneration in both healthy and diabetic rats. Diabetes was induced through single subcutaneous injection of aqueous alloxan at the dose of 100 mg/kg. Twenty four albino rats were divided into four groups; healthy control, diabetic control, healthy treated and diabetic treated. Treated groups received 100 mg/kg of d-α-tocopherol and d-δ-TRF each, orally, daily for three weeks. Through a horizontal mid-thigh skin incision and splitting of the fascia gluteus maximus was approached and crushed with Kocher’s forceps. Skin wound was closed with an absorbable suture. The crush-induced degenerative and regenerative changes in the muscle were studied by assessing the histological features, histomorphological measurements and biochemical analyses at the end of 3rd weeks. One- way ‘ANOVA’ and Student’s t-test were used for statistical analysis. All results revealed that the vitamin E isoforms have potency to maintain glycemic level, improve the antioxidant capacity and hasten the process of regeneration, revascularization, reinnervation and connective tissue remodeling in skeletal muscle after crush injury. It is therefore, concluded that the vitamin E isoforms are useful nutritional supplements for skeletal muscle functional and structural recovery in both healthy and diabetics.

Normal wound healing involves sequence of events which is believed to be altered in diabetes due to hyperglycemia, infection and oxidative stress. The latter may be reduced by antioxidants which neutralize the chain formation of free radicals. Vitamin E is a well-known antioxidant and has saturated tocopherols and unsaturated tocotrienols. The most active form being the α-tocopherol. The present study was designed to explore the combined effect of d-α-tocopherol and d-δ-tocotrienol rich fraction (d-δ-TRF) on wound healing process in both healthy and alloxan-induced diabetic rats. Diabetes was induced with alloxan (100 mg/kg S. C). Twenty four albino rats were divided into four groups; healthy control, diabetic control, healthy treated and diabetic treated. Treated groups received 100 mg/kg of d-α-tocopherol and d-δ-TRF each orally and daily for 3 weeks. Under general anesthesia, full-thickness excisional skin wounds were created on the dorsal surface of thoracic region. Macroscopic and microscopic features of wound healing stages were recorded at weekly intervals and biochemical parameters were estimated at the end of 3 weeks. It was observed that as compared to control in the treated group there was early reappearance of epidermal and dermal components, reduced serum creatinine level, increased serum antioxidant status and total protein content and controlled glycemic status. It is concluded that oral co-administration of d-α-tocopherol and d-δ-TRF promotes skin wound healing in both healthy and diabetic rats through its antioxidant potency, therefore suggested that vitamin E isoforms hold promising future in the effective management of wounds in both otherwise healthy and diabetics.

Background: Delayed muscle growth and regeneration of skeletal muscle in diabetics is believed to be due to diabetic myopathy because of alteration in the skeletal muscle homeostatis. Since vitamin E is a natural antioxidant and is also important for the integrity of sarcolemma, the present study was designed to explore the muscle regenerative potency of d-δ-tocotrienol-rich fraction (d-δ-TRF) on crushed skeletal muscle in healthy and diabetic rats. Materials and Methods: Diabetes was induced through single subcutaneous injection of alloxan (100 mg/kg). Twenty-four albino rats were divided into four groups; healthy control, diabetic control, healthy treated, and diabetic treated. Treated groups received injections orally, daily (200 mg/kg) for 3 weeks. A horizontal skin incision was made on the shaved right mid-thigh region, by splitting the fascia between gluteus maximus and tensor fascia lata, and gluteus maximus was crushed with Kocher’s forceps. Skin wound was closed with an absorbable suture. The crushed muscle changes were studied by assessing the histopathological features, histomorphological measurements, and biochemical analyses on 3rd week following induction of injury. One-way “ANOVA” followed by Tukey’s test and Student t-test were used for statistical analysis of data. Results: Results obtained through various methods indicate that the d-δ-TRF treated groups have controlled glycemic status, improved antioxidant capacity, faster revascularization, re-innervation, regeneration of myofibers, and connective tissue remodeling. Conclusion: It is, therefore, concluded that the d-δ-TRF is a beneficial nutritional adjuvant for skeletal muscles’ structural and functional recovery after crushed injury in both healthy and diabetics.

Aim: The preparation and characterization of a novel escheriosomal nanoparticle formulation of a potent anticancer conjugate, 2,6-diisopropylphenol-linoleic acid (2,6P–LA), and evaluation of its anticancer efficacy against diethyl nitrosamine-induced hepatocellular carcinoma (HCC) in BALB/c mice. Materials & methods: Escheriosomized 2,6P–LA nanoparticles were characterized for size, zeta-potential, entrapment efficiency, release kinetics and in vivo toxicity. Their anticancer potential was evaluated on the basis of survival, DNA fragmentation, caspase-3 activation, western blot analysis of apoptotic factors and histopathological changes in hepatocytes of treated animals. Results: The escheriosomized 2,6P–LA nanoparticles exhibited low toxicity, biocompatibility and bioavailability. As revealed by apoptosis induction, survival rate, expression profiles of Bax, Bcl-2 and caspase-9, escheriosomized 2,6P–LA nanoparticles were more effective in the treatment of HCC than the free form of 2,6P–LA in experimental animals. Conclusion: 2,6P–LA-bearing escheriosome nanoparticles are effective in suppressing HCC in mice. Original submitted 17 January 2012; Revised submitted 27 August 2012; Published online 14 January 2013

Recent years have witnessed importance of histamine in immunopathophysiological implications in several diseases. Moreover, its role in development of disease pathology is still being elucidated. Accumulating evidences have highlighted that histamine has the possible role in pathology of autoimmunity by modulating the cytokine network and influence T-lymphocytes (Th1 and Th2) balance, and antibody isotype switching. Hence, there is a real need to search for newer role of histamine in disease development. In this review, we will highlight histamine role in pathology of autoimmunity and its mechanism, and also histamine role in pathogenesis of autoimmune, allergic, inflammatory and malignant diseases such as chronic urticaria (CU), atopic dermatitis (AD), autoimmune myocardium (AM) and multiple sclerosis (MS) & experimental autoimmune encephalomyelitis (EAE); allergic rhinitis, anaphylaxis (acute) and asthma; atherosclerosis; and malignant melanoma, respectively. There are several steps in the autoimmune attack/allergic march where histamine might play an important role.

Progressive anterograde axonal degeneration is known to follow after transection of the axon from the soma, which to some extent correlates with the passage of time after the lesion. However, the minimum time required for such changes to begin remains unresolved. In this study, 20 young adult rabbits of either sex underwent experimental monocular enucleation (left eye) under general anaesthesia. Left optic nerves from such animals were treated as experimental and those from either side of non-operated animals served as controls. Animals were sacrificed postoperatively at periods ranging from 12 h to 3 months. Brains were fixed with 10% formalin and Karnovsky fixatives by an intracardiac perfusion method. Light microscopy of 8-µm paraffin sections and 0.5-µm araldite sections from the optic nerves did not reveal any changes at 12 h. At 24 h, focal minute cavities appeared across the optic nerves. Those nerves from late postoperative stages revealed such cavities with increasing dimensions, disarray of fascicular organization, fragmentation, ovoid formation and finally dissolution of the myelin sheaths. There was an appreciable increase in the number, size and aggregation of glia cells. The debris of degeneration remained prominent even 3 months after enucleation. Electron microscopy revealed splitting of myelin, intramyelinic and periaxonal oedema and occurrence of amorphous and electron-dense materials in the degenerating nerve fibres. It was concluded that while the optic nerve showed degenerative changes as early as 24 h after enucleation, debris of degeneration was only partly removed even after 3 months.