Biomedical subjects

Sameer Sharma

Publications and source records attributed to Sameer Sharma.

At least 19 recordsLinked to original sources

PubMed2007

Effect of insulin and its combination with resveratrol or curcumin in attenuation of diabetic neuropathic pain: participation of nitric oxide and TNF-alpha.

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, is recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of insulin and its combinations with resveratrol and curcumin in attenuating diabetic neuropathic pain. The study also aimed to examine the effect of these combinations on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels in streptozotocin (STZ) induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights compared with control mice. Chronic treatment with insulin (10 IU/kg/day, s.c.) and its combinations with antioxidants (resveratrol 20 mg/kg or curcumin 60 mg/kg, p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. There was a significant inhibition of TNF-alpha and NO levels when these drugs were given in combination compared with their effects per se. These results indicate an antinociceptive activity of resveratrol and curcumin and point towards the beneficial effect of these combinations with insulin in attenuating diabetic neuropathic pain, possibly through the participation of NO and TNF-alpha.

Animals↗

PubMed2007

Effect of resveratrol, a polyphenolic phytoalexin, on thermal hyperalgesia in a mouse model of diabetic neuropathic pain.

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus, has been recognized as one of the most difficult types of pain to treat. The underlying mechanisms of painful symptoms may be closely associated with hyperglycaemia but a lack of the understanding of its proper aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of resveratrol on diabetic neuropathic pain and to examine its effect on serum tumour necrosis factor-alpha (TNF-alpha) and whole brain nitric oxide (NO) release. Four weeks after a single intraperitoneal injection of streptozotocin (STZ, 200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights when compared with control mice. Daily treatment with resveratrol (5, 10 and 20 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of STZ injection significantly attenuated thermal hyperalgesia. Resveratrol also decreased the serum TNF-alpha levels and whole brain NO release in a dose-dependent manner. These results point towards the potential of resveratrol in attenuating diabetic neuropathic pain.

Analgesics, Non-Narcotic↗

PubMed2006

Characterization of neutropenic fever in patients receiving first-line adjuvant chemotherapy for epithelial ovarian cancer.

OBJECTIVES: Limited information is available on the incidence and characteristics of neutropenic fever (NF) in patients receiving contemporary regimens for epithelial ovarian cancer (EOC). We examined this issue in patients receiving first-line adjuvant chemotherapy with platinum- and paclitaxel-based regimens at a major cancer institute. METHODS: Charts of patients with EOC at a single institute from 1998 through 2002 were reviewed. Data were collected on the incidence and duration of NF, duration of hospitalization and fever, cultures, antibiotic and chemotherapy regimen, and type of debulking procedure. RESULTS: 140 patients were treated for EOC. 125 patients received first line chemotherapy. 15 episodes of NF were observed. Mean duration of neutropenia and fever was 2.33 and 3.07 days respectively. 9 of 15 (60%) NF episodes occurred after cycle 1. Cultures were positive in 7 of 15 patients (47%). Organisms most frequently recovered were bowel-derived. 8 patients (53%) had bowel resections, and 15 patients (100%) had radical or supraradical procedures. There was a correlation between incidence of NF and type of procedure (P = 0.01) and stage of EOC (P = 0.04). There was no correlation between NF and elderly age, medical comorbidities, and postoperative complications. CONCLUSIONS: The rate of NF was higher than previously reported. NF occurred most frequently after cycle 1. NF patients were of advanced stage that had undergone more aggressive surgery and had bowel resections. Our data suggest that patients with advanced EOC who undergo more radical procedures should be identified as high risk for developing NF in early cycles.

Adult↗

PubMed2006

Low density multiparticulate system for pulsatile release of meloxicam.

A blend of floating and pulsatile principles of drug delivery system would have the advantage that a drug can be released in the upper GI tract after a definite time period of no drug release. A multiparticulate floating-pulsatile drug delivery system was developed using porous calcium silicate (Florite RE) and sodium alginate, for time and site specific drug release of meloxicam. Meloxicam was adsorbed on the Florite RE (FLR) by fast evaporation of solvent from drug solution containing dispersed FLR. Drug adsorbed FLR powder was used to prepare calcium alginate beads by ionotropic gelation method, using 3(2) factorial design. Developed formulations were evaluated for yield, entrapment efficiency, image analysis, surface topography, mechanical strength, apparent density, buoyancy studies and dissolution studies. Entrapment efficiency of different formulations varied from 70% to 94%. Formulations show a lag period ranging from 1.9 to 7.8 h in acidic medium followed by rapid release of meloxicam in simulated intestinal fluid USP, without enzymes (SIF). Complete drug release in SIF occurred in less than 1h from the formulations. The size of beads varied from 2.0 to 2.7 mm for different batches. Prepared beads were spherical with crushing strength ranging from 182 to 1,073 g. Floating time was controlled by density of beads and hydrophobic character of drug. A pulsatile release of meloxicam was demonstrated by a simple drug delivery system which could be useful in chronopharmacotherapy of rheumatoid arthritis.

Alginates↗

PubMed2006

Curcumin attenuates thermal hyperalgesia in a diabetic mouse model of neuropathic pain.

Diabetic neuropathic pain, an important microvascular complication in diabetes mellitus is recognised as one of the most difficult types of pain to treat. A lack of the understanding of its aetiology, inadequate relief, development of tolerance and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain. The aim of the present study was to explore the antinociceptive effect of curcumin and its effect on tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) release in streptozotocin induced diabetic mice. Four weeks after a single intraperitoneal injection of streptozotocin (200 mg/kg), mice were tested in the tail immersion and hot-plate assays. Diabetic mice exhibited significant hyperalgesia along with increased plasma glucose and decreased body weights as compared with control mice. Chronic treatment with curcumin (15, 30 and 60 mg/kg body weight; p.o.) for 4 weeks starting from the 4th week of streptozotocin injection significantly attenuated thermal hyperalgesia and the hot-plate latencies. Curcumin also inhibited the TNF-alpha and NO release in a dose dependent manner. These results indicate an antinociceptive activity of curcumin possibly through its inhibitory action on NO and TNF-alpha release and point towards its potential to attenuate diabetic neuropathic pain.

Analgesics↗

PubMed2006

Study of formulation variables on properties of drug-gellan beads by factorial design.

The aim of the present study was to obtain cross-linked calcium-gellan beads containing diclofenac sodium as model drug, using full 3(3) factorial design. Drug quantity, pH of cross-linking solution, and speed of agitation were selected as variables for factorial design. The resultant beads were evaluated by scanning electron microscopy (SEM), percent yield, entrapment efficiency, micromeritic properties, swelling and drug release studies. The drug-loaded beads were spherical with size range of 0.85-1.8 mm. Percent yield and entrapment efficiency of various batches were in the range of 86.48-98.28% w/w and 72.52-92.74% w/w, respectively. Calcium-gellan beads containing diclofenac sodium showed pH-dependent swelling and drug release properties. Swelling and drug release were significantly higher in pH 7.4 phosphate buffer than 0.1N HCl. The swelling ratio for beads was up to 22 and 3 for phosphate buffer and 0.1N HCl, respectively. Cumulative diclofenac sodium release from calcium-gellan beads was 12-35% in 0.1N HCl within 2 h, whereas complete drug release was observed within 3-4 h in pH 7.4 phosphate buffer.

Calcium Chloride↗

PubMed2006

Curcumin, the active principle of turmeric (Curcuma longa), ameliorates diabetic nephropathy in rats.

Chronic hyperglycaemia in diabetes leads to the overproduction of free radicals and evidence is increasing that these contribute to the development of diabetic nephropathy. Among the spices, turmeric (Curcuma longa) is used as a flavouring and colouring agent in the indian diet every day and is known to possess anti-oxidant properties. The present study was designed to examine the effect of curcumin, a yellow pigment of turmeric, on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. Four weeks after STZ injection, rats were divided into four groups, namely control rats, diabetic rats and diabetic rats treated with curcumin (15 and 30 mg/kg, p.o.) for 2 weeks. Renal function was assessed by creatinine, blood urea nitrogen, creatinine and urea clearance and urine albumin excretion. Oxidative stress was measured by renal malonaldehyde, reduced glutathione and the anti-oxidant enzymes superoxide dismutase and catalase. Streptozotocin-injected rats showed significant increases in blood glucose, polyuria and a decrease in bodyweight compared with age-matched control rats. After 6 weeks, diabetic rats also exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance and proteinuria, along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key anti-oxidant enzymes. Chronic treatment with curcumin significantly attenuated both renal dysfunction and oxidative stress in diabetic rats. These results provide confirmatory evidence of oxidative stress in diabetic nephropathy and point towards the possible anti-oxidative mechanism being responsible for the nephroprotective action of curcumin.

Animals↗

PubMed2006

Seroprevalence of leptospirosis among high-risk population of Andaman Islands, India.

Leptospirosis is a severe spirochetal zoonosis in the world. It is considered an occupational disease of persons engaged in agriculture, sewage works, forestry, and animal slaughtering. A study was conducted with an objective of assessing the seroprevalence of leptospirosis among the high-risk groups of Andaman Islands. A total of 611 sera samples from different high-risk populations were collected and tested by microscopic agglutination test (MAT). Genetic characterization of the isolate was done by randomly amplified polymorphic DNA (RAPD) fingerprinting, and serological characterization was done using monoclonal antibody technique. Antibodies to leptospires were detected in 322 samples giving an overall seroprevalence of 52.7%. The seroprevalence was highest among agriculture workers (62.5%) followed by sewage workers (39.4%), animal handlers (37.5%), forest workers (27.3%), and butchers (30.0%). Seroprevalence among control population was 14.7%, which was comparatively less than that of the high-risk population groups. Subject sera were most commonly reacted with organisms of the serogroup Grippotyphosa followed by Australis, and the pattern was similar in control group. Four leptospires were isolated from agriculture workers who were admitted to the public health center (PHC) with complaints of fever and body ache. Human isolates were compared with two rodent (Rattus norvegicus) isolates from the same area of agriculture workers to get initial information about the transmission cycle of leptospirosis in the study community. Randomly amplified polymorphic DNA fingerprinting pattern of the strains recovered from the rodents and human patients were identified as belonged to genomo-species Leptospira interrogans. The antigenic characterization of the strains recovered from them belonged to serovar Valbuzzi of serogroup Grippotyphosa. The study showed that people engaged in high-risk activities such as agriculture, sewage cleaning, animal handling, animal slaughtering, and forestry are frequently exposed to leptospirosis, and hence control strategies targeting these populations could be more effective.

Adult↗

PubMed2006

Resveratrol, a polyphenolic phytoalexin attenuates thermal hyperalgesia and cold allodynia in STZ-induced diabetic rats.

The effects of resveratrol, a polyphenolic phytoalexin present in red wine have been investigated on hyperalgesia and cold allodynia in streptozotocin (STZ) induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of streptozotocin (65mg/kg). After 4-weeks of STZ injection, diabetic rats exhibited a significant thermal hyperalgesia and cold allodynia along with increased plasma glucose and decreased body weights as compared with controls rats. Chronic treatment with resveratrol (10mg/kg orally) from week 4 to week 6 significantly attenuated the cold allodynia and thermal hyperalgesia. The results emphasize the role of oxidative stress in development of hyperalgesia and cold allodynia in diabetic animals and point towards the potential of resveratrol as an adjuvant therapy for the prevention and treatment of diabetic neuropathy.

Animals↗

PubMed2006

OY-TES-1 expression and serum immunoreactivity in epithelial ovarian cancer.

OY-TES-1 is a novel target that belongs to the family of 'cancer/testis' (CT) antigens. Our goal was to examine the expression and immunogenicity of OY-TES-1 in epithelial ovarian cancer (EOC) to determine its potential as a target for vaccine therapy. OY-TES-1 expression was determined by one-step reverse transcriptase PCR on 100 EOC samples, 5 EOC cell lines, and a panel of normal tissues. Immunohistochemistry (IHC) was performed on the same panel of EOC tissues. Sera from a sub-group of patients were tested for OY-TES-1 antibody by ELISA. Thymus and leukocytes were weakly positive for OY-TES-1 while the remaining 5 normal tissues were negative. Expression of OY-TES-1 by either RT-PCR and/or IHC was demonstrable in 69/100 (69%) tumors. Humoral immunity to OY-TES-1 was demonstrated in 1/10 (10%) serum samples from patients whose tumors expressed the antigen. The median follow-up of the patient population was 34 months. There was no correlation between antigen expression and stage, grade, histology and survival. OY-TES-1 is expressed in 69% of patients with EOC, is absent from normal ovarian tissue, and a proportion of patients show evidence of a specific humoral immune response. These findings make OY-TES-1 an attractive target for antigen-specific immunotherapy in EOC.

Adult↗

PubMed2005

Adsorption of meloxicam on porous calcium silicate: characterization and tablet formulation.

The purpose of the present study was characterization of microparticles obtained by adsorption of poorly water soluble drug, meloxicam, on a porous silicate carrier Florite RE (FLR) and development of a tablet formulation using these microparticles, with improved drug dissolution properties. The study also reveals the use of FLR as a pharmaceutical excipient. Meloxicam was adsorbed on the FLR in 2 proportions (1:1 and 1:3), by fast evaporation of solvent from drug solution containing dispersed FLR. Drug adsorbed FLR microparticles were evaluated for surface topography, thermal analysis, X-ray diffraction properties, infrared spectrum, residual solvent, micromeritic properties, drug content, solubility, and dissolution studies. Microparticles showed bulk density in the range of 0.10 to 0.12 g/cm(3). Dissolution of drug from microparticles containing 1:3, drug:FLR ratio was faster than microparticles containing 1:1, drug:FLR ratio. These microparticles were used for formulating directly compressible tablets. Prepared tablets were compared with a commercial tablet. All the prepared tablets showed acceptable mechanical properties. Disintegration time of prepared tablets was in the range of 18 to 38 seconds, and drug dissolution was much faster in both acidic and basic medium from prepared tablets as compared with commercial tablet. The results suggest that FLR provides a large surface area for drug adsorption and also that a reduction in crystallinity of drug occurs. Increase in surface area and reduction in drug crystallinity result in improved drug dissolution from microparticles.

Adsorption↗

PubMed2005

Resveratrol, a polyphenolic phytoalexin, attenuates diabetic nephropathy in rats.

Diabetic nephropathy is a serious microvascular complication and one of the main causes of end-stage renal disease. Various studies have revealed that increased oxidative stress is a major pathophysiological mechanism which is involved in the etiology of diabetic nephropathy. Resveratrol, a polyphenolic phytoalexin present in red wine, is known to possess potent antioxidant properties and thus we aimed to examine its effect on renal function and oxidative stress in streptozotocin (STZ)-induced diabetic rats. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in rats. After 4 weeks of STZ injection, rats were divided into four groups: the control rats, diabetic rats and diabetic rats treated with resveratrol (5 and 10 mg/kg, orally) respectively from week 4 up till week 6. At the termination of the experiments, urine albumin excretion, urine output, serum creatinine, blood urea nitrogen, creatinine and urea clearance were measured. The levels of the renal oxidative stress markers malonaldehyde and glutathione and the antioxidant enzymes superoxide dismutase and catalase were measured in kidney homogenate. STZ-injected rats showed significant increases in blood glucose, polyuria, proteinuria and a decrease in body weight compared with age-matched control rats. After 6 weeks, diabetic rats exhibited renal dysfunction, as evidenced by reduced creatinine and urea clearance, and proteinuria along with a marked increase in oxidative stress, as determined by lipid peroxidation and activities of key antioxidant enzymes. Treatment with resveratrol significantly attenuated renal dysfunction and oxidative stress in diabetic rats. The present study reinforces the important role of oxidative stress in diabetic kidney and points towards the possible antioxidative mechanism being responsible for the renoprotective action of resveratrol.

Animals↗

PubMed2005

Immunogenic and antigenic properties of recombinant soluble glycoprotein of rabies virus.

Rabies virus glycoprotein is a type I transmembrane protein exposed on the surface on the mature virus particle that induces virus neutralizing antibodies. In the present study, 60 amino acid C-terminal hydrophobic anchor (transmembrane) and cytoplasmic domains of glycoprotein were deleted from full-length glycoprotein and fused with polyhistidine tag. The N-terminal viral signal peptide was also replaced with CD33 signal peptide for efficient secretion in mammalian cells. Following transfection of Madin Darby bovine kidney (MDBK) cells with plasmid encoding this soluble form of glycoprotein, polyclonal populations of stably transfected resistant cells were obtained after G418 selection. The protein was expressed as a glycosylated protein and secreted outside the cells utilizing N-terminal CD33 signal peptide. The secreted soluble glycoprotein was purified from cell culture supernatant by Ni--agarose affinity chromatography utilizing C-terminal polyhistidine tag. Like full-length glycoprotein, the expressed recombinant soluble glycoprotein was found to be immunogenic when injected in rabbits. In this study, we have assessed the potential of recombinant soluble glycoprotein as diagnostic antigen in ELISA and found that this recombinant protein can be used as diagnostic antigen in ELISA for detecting anti-glycoprotein antibodies in immunized host.

Animals↗

PubMed2005

Safety and efficacy of cytoreductive surgery for epithelial ovarian cancer in elderly and high-risk surgical patients.

OBJECTIVE: Surgery is the cornerstone of management in ovarian cancer. However, in high-risk and elderly patients there is a tendency for less aggressive surgery upfront. The aim of this study was to review cytoreductive surgery, with focus on complications and outcomes in patients with multiple surgical risk factors. STUDY DESIGN: Charts of patients with ovarian cancer from 1998 to 2002 were retrospectively reviewed. RESULTS: One hundred and forty patients were treated for ovarian cancer. Sixty-three patients (45%) were elderly (> or =65 years), and 69 patients (49%) had comorbidities. Optimal debulking (< or =1 cm) was achieved in 123 patients (88%). There was no significant relation between complications and type of procedure, elderly age, comorbidities, or transfusions. Optimally debulked patients had a significantly longer survival than patients with suboptimal debulking (P < .001). CONCLUSION: Aggressive optimal cytoreduction can be achieved in the majority of patients with multiple surgical risk factors and is associated with a low complication rate.

Adult↗

PubMed2005

A rare female genital tract tumor: benign granular cell tumor of vulva: case report and review of the literature.

BACKGROUND: The granular cell tumor (GCT) of vulva is a rare female genital tract tumor. CASE: A 59-year-old female was incidentally noted to have a 1-cm sized lump in her left labium majus that subsequently increased in size to approximately 4 cm. The mass was totally excised under general anesthesia. Her postoperative follow-up was uneventful. Histologic examination of the tumor showed sheets and clusters of infiltrating tumor cells with morphologic features consistent with granular cell tumor. CONCLUSION: Although benign and slow growing, it has a tendency for recurrence and can cause morbidity and mortality when presenting with multicentric or multiple organ involvement due to the lack of effective systemic therapy. Therefore, clinicians and pathologists should be aware of its clinical and histopathologic features.

Female↗

PubMed2005

A-kinase anchoring protein 3 messenger RNA expression correlates with poor prognosis in epithelial ovarian cancer.

OBJECTIVES: Cancer-testis (CT) antigens are expressed in tumors but not normal tissues except the testis and could be targets for vaccine therapy in epithelial ovarian cancer (EOC). A-kinase anchoring protein 3 (AKAP-3) is a novel member of the CT antigen family. The aim of this study was to examine the expression of AKAP-3 in EOC and correlate with clinico-pathologic characteristics. METHODS: One step RT-PCR was performed with RNA from normal and ovarian cancer cell lines and 74 epithelial ovarian tumor tissues. AKAP-3-specific PCR product was amplified. The distribution of AKAP-3 expression and clinico-pathologic variables was analyzed. Survival distributions were estimated, and multivariate analyses were performed. RESULTS: AKAP-3 mRNA expression was demonstrated in 43/74 (58%) of the ovarian cancer specimens. AKAP-3 was expressed in normal testis, but not in other normal tissues. AKAP-3 expression significantly correlated with increased likelihood of residual tumor (P = 0.005), but no increase in the likelihood of recurrence or persistent disease (P = 0.06). Patients with AKAP-3 mRNA expression were found to have a significantly poorer overall survival (median 50 months) compared with patients without AKAP-3 expression (median not reached) (P = 0.007). Multivariate analysis of AKAP-3 expression, residual disease, and response to frontline chemotherapy found response to be the strongest predictor of overall survival (P = 0.012). CONCLUSIONS: Our data demonstrate that AKAP-3 is expressed at high frequency in patients with EOC. Since AKAP-3 demonstrates tumor-restricted expression and appears to be associated with worse overall survival, it could represent an attractive target for antigen-specific immunotherapy in EOC.

A Kinase Anchor Proteins↗

PubMed2005

Targeted therapy for epithelial ovarian cancer.

Ovarian cancer is the leading cause of death in women with gynecological malignancies and overall survival for patients with advanced epithelial ovarian cancer (EOC) remains poor. The majority of patients recur after initial treatment. A strategy for improving outcome is to minimise recurrence via targeted therapy in patients after front-line therapy, or more appropriately as consolidation therapy. EOC represents an attractive target because of the biology of the disease and that the bulk of disease occurs in the peritoneal cavity. To initiate targeted therapy, a candidate target must be identified. Innovative approaches via targeted therapy to control metastatic residual EOC are currently under investigation. The targets are molecules and pathways, on which cancer cells depend to proliferate, invade, metastasise and prevent apoptosis. Potential targeted therapies include: proapoptototic therapy, suicide gene therapy, signal transduction, antiangiogenesis, immunotherapy and cytokine therapy. The utilisation of these targets in the clinic demands carefully conducted, well-coordinated but discovery-oriented translational research in the form of clinical trials that can quickly assess alternative strategies or combination of strategies that could result in clinical benefit. Therefore, targeted therapy for epithelial ovarian cancer, especially after complete response to standard regimens, represents a paradigm whose time has come to be nurtured.

Antineoplastic Agents↗

PubMed2005

Possible analgesic and anti-inflammatory interactions of aspartame with opioids and NSAIDs.

The purpose of the present study was to investigate analgesic and anti-inflammatory properties of aspartame, an artificial sweetner and its combination with various opioids and NSAIDs for a possible synergistic response. The oral administration of aspartame (2-16mg/kg, po) significantly increased the pain threshold against acetic acid-induced writhes in mice. Co-administration of aspartame (2mg/kg, po) with nimesulide (2 mg/kg, po) and naproxen (5 mg/kg, po) significantly reduced acetic acid-induced writhes as compared to effects per se of individual drugs. Similarly when morphine (1 mg/kg, po) or pentazocine (1 mg/kg, po) was co-administered with aspartame it reduced the number of writhes as compared to their effects per se. Aspartame (4,8,16 mg/kg, po) significantly decreased carrageenan-induced increase in paw volume and also reversed the hyperalgesic effects in rats in combination with nimesulide (2 mg/kg, po). The study indicated that aspartame exerted analgesic and anti-inflammatory effects on its own and have a synergistic analgesic response with conventional analgesics of opioid and non-opioid type, respectively.

Acetic Acid↗