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Cotard's syndrome is a rare syndrome, characterized by the presence of nihilistic delusions. The syndrome is typically related to depression and is mostly found in middle-aged or older people. A few cases have been reported in young people with 90% of these being females. We present a case of a young pregnant woman suffering from Cotard's syndrome. This is the first report of this syndrome in a pregnant woman. The case was diagnosed late, due to lack of awareness of psychiatric problems in primary care physicians resulting in undue suffering, loss of precious time and resources for the patient. Besides highlighting the rare combination of pregnancy and Cotard's syndrome this report delineates the difficulties faced by patients with such symptoms in a low resource setting.

Background and Aim: Recently, statins have appeared to have additional benefits beyond their lipid lowering effects, which has led to the interest in the use of this class of drugs outside the realm of cardiovascular disease. Simvastatin (SIM) is a commonly prescribed statin with anti-inflammatory and antioxidant properties. Excessive generation of oxygen-derived free radicals (ODFR) and proinflammatory mediators has been implicated in the pathogenesis of gastric ulcers. This investigation aimed to study the effect of SIM on experimentally induced gastric acid secretion and ulcer formation., Methods: Adult Wistar rats were divided into experimental groups containing six animals. Acid secretion studies were undertaken using pylorus-ligated rats pretreated with SIM (20, 40, and 60 mg/kg). The effect of orally administered SIM was also studied on indomethacin- and ethanol-induced gastric ulcers. The levels of myeloperoxidase (MPO), non-protein sulfhydryls (NP-SH), nitric oxide (NO), antioxidant enzymes, and gastric wall mucus were measured in the glandular stomach of rats following ethanol-induced gastric lesions., Results: Administration of SIM significantly and dose-dependently inhibited the volume of gastric secretion and the acidity. Pretreatment with SIM significantly reduced the formation of indomethacin- and ethanol-induced gastric lesions. The antiulcer activity of SIM was associated with significant attenuation of adverse effects of ethanol on gastric wall mucus, NP-SH and MPO. SIM modified the gastric NO levels and reversed the ethanol-induced decrease in glutathione-S-transferase and increase in superoxide dismutase and catalase., Conclusions: These findings clearly suggest the involvement of proinflammatory agents and ODFR in the pathogenesis of gastric lesions. The gastroprotective effects of SIM are mediated by inhibition of neutrophils activity, reduction of oxidative stress, and maintenance of vascular integrity. This study was conducted in rats; its relevance to human gastric ulcers is not known and warrants further study.

Background: The mastectomy site is usually assessed by clinical examination and ultrasonography for recurrence of breast cancer, although post-surgical and radiotherapy changes limit the accuracy of these methods. MRI has been used successfully but it remains an expensive modality and may not be readily available. Scintimammography is an alternative method which has the advantage of not being affected by post-operative morphological changes., Aim: To evaluate the usefulness of planar Tc-MIBI scintimammography and supine Tc-MIBI SPECT in the detection of chest wall recurrence post-mastectomy., Methods: The study population comprised of 26 patients (mean age, 47.15 years; median age 47 years; age range, 22-77 years) with suspected chest wall recurrence of breast cancer on clinical examination. All patients received a 740-1000 MBq bolus i.v. injection of Tc-MIBI preferably in the pedal vein. At 5-10 min post-injection planar images were obtained in the prone lateral and supine anterior positions using a double-head gamma camera. After planar imaging supine SPECT was performed (64 projections, 64x64 matrix, 30 s.frame). MIBI uptake was scored as follows: 1 = normal uptake (compared with contralateral side); 2 = focal low uptake (equivocal); and 3 = focal high uptake (positive). All patients underwent excision biopsy or FNAC for tissue diagnosis. FNAC was considered sufficient if unequivocally positive., Results: For the 26 patients, planar scintimammography was found true positive in 14 and true negative in seven. The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 78%, 87.5%, 93%, 64% and 81%, respectively (P<0.001). SPECT showed a significantly higher overall sensitivity than planar imaging (89% vs. 78%; P<0.001). SPECT and planar imaging showed the same specificity (87.5%). SPECT showed a significantly higher negative predictive value and accuracy than planar imaging (78% vs. 64% and 88% vs. 81%, respectively; P<0.05)., Conclusion: Scintimammography is a reliable diagnostic tool and appears accurate in the detection of chest wall recurrence. SPECT shows high positive predictive value and aids in the diagnosis of the chest wall recurrence with greater confidence.

Purpose: This study was aimed to develop a simple and user-friendly software for fast and accurate computation of normal tissue complication probability (NTCP) in accordance with the Lyman model., Materials and Methods: The software CalcNTCP has been developed in Visual Basic and is equipped with two functional modes. Mode 1 is based on pre-stored values of various parameters for 27 different organ systems and the user has only to input the values of volume fraction (v) and radiation dose (D), whereas Mode 2 is designed for the customized entries., Results: The results of software validation have demonstrated that CalcNTCP is more efficient and time-saving as compared to manual or semi-manual procedures. The shapes and locations of representative survival curves generated by CalcNTCP-based computations for various radiation doses (10 - 100 Gy) and reference volumes (0.33 - 1.00) absolutely matched with optimal curves., Conclusion: CalcNTCP is a simple, fast and accurate tool for the computation of NTCP with a direct implication in the evaluation or optimization of radiotherapy treatment plans.

Overdose of oral medications can be a major concern. This article reviews the clinical presentations, toxic dosages, adverse effects, and the recommended treatments for the most commonly used oral medications in dentistry. Clinicians need to be aware of the toxicities and adverse effects of the most commonly used oral medications, and recognize the signs and symptoms as early as possible for expedient treatment and referral.

Background: Compared to steroids non-steroidal anti-inflammatory drugs offer comparable anti-inflammatory action without ocular side-effects., Aim: To compare the anti-inflammatory effect and effect on IOP (Goldmann) of topical diclofenac 0.1% with dexamethasone 0.1% after strabismus surgery., Design: Prospective, randomized, double-blind, single-center, clinical trial., Materials and Methods: Forty-three cases of constant horizontal strabismus, qualifying for standard uniocular recession-resection surgery on two horizontal rectus muscles were randomized to either the dexamethasone or diclofenac group. They were excluded if they had previous ocular surgery, recently used anti-inflammatory drugs and had a neurological, systemic or an ocular inflammatory condition. In addition all received ciprofloxacin 0.3% four times daily. Assessment was done on the first postoperative day and at two and four weeks. The inflammatory characteristics graded from nil (0) to severe (3) were: discomfort, chemosis, injection, discharge and drop-intolerance. Their sum provided the total inflammatory score (TIS)., Results: Dexamethasone group (n=21) was comparable in age, gender, preoperative IOP, strabismus, anesthesia administered and baseline IOP, to diclofenac (n=22). There were no significant differences in the inflammatory characteristics and TIS. The dexamethasone group had IOP significantly higher at two weeks (95% CI 0.17 to 3.25) and four weeks (95% CI 1.09 to 4.24) compared to diclofenac group and the net change of IOP at four weeks (95% CI 0.60 to 3.14). Compared to the baseline IOP., Conclusion: Topical diclofenac is comparable to dexamethasone in providing anti-inflammatory and analgesic effect with the advantage of significantly lesser IOP rise and should be preferred after strabismus surgery.

Unlabelled: Our objective in this study was to evaluate whether measurement of quantitative uptake of (99m)Tc-methylene diphosphate (MDP) and (99m)Tc-hexamethylpropyleneamine oxime (HMPAO) white blood cells (WBCs) is useful in detecting osteomyelitis in peripheral bony lesions., Methods: Twenty-four patients (12 men and 12 women; age range, 25-72 y) were referred for imaging because of clinically suspected osteomyelitis. They had a traumatic fracture (n = 10), knee prosthesis (n = 5), hip prosthesis (n = 2), diabetic foot (n = 4), or chronic osteomyelitis (n = 3). Three-phase bone scanning and (99m)Tc-HMPAO WBC studies were performed on all patients within the same week. Regions of interest were drawn over the abnormal bony sites and the contralateral normal sites, and the abnormal-to-normal uptake ratios (A/N ratios) were obtained for both studies., Results: All patients had abnormal findings on 3-phase bone scanning, whereas 17 (71%) had abnormal findings on (99m)Tc-HMPAO WBC studies, of which 15 were confirmed to be true-positive. In those 15 patients, the mean A/N ratios for (99m)Tc-MDP and (99m)Tc-HMPAO WBC were 3.0 +/- 1.6 (range, 1.3-6.2) and 1.8 +/- 0.3 (range, 1.4-2.2), respectively. In the other 9 patients, whose scan results were clinically confirmed to be true-negative, the mean A/N ratios for (99m)Tc-MDP and (99m)Tc-HMPAO WBC were 2.1 +/- 1.2 and 1.2 +/- 0.2, respectively. In the group with a (99m)Tc-MDP A/N ratio greater than 2 (n = 15), 87% (13/15) had a high (99m)Tc-HMPAO WBC A/N ratio (>1.5), including 2 that were false-positive. In the remaining 2 patients, one with chronic osteomyelitis and the other with a recent hip prosthesis, (99m)Tc-HMPAO WBC ratios were normal. In the group with a bone A/N ratio of less than 2 (n = 9), only 4 patients (44%) were true-positive for acute osteomyelitis., Conclusion: (99m)Tc-MDP bone scanning alone, with an A/N ratio of more than 2, is useful in detecting osteomyelitis in violated bone except in the case of a recent hip prosthesis or chronic osteomyelitis.

Plants are an abundant source of medicinal compounds, some of which are useful in combating free radical-mediated oxidative stress. In the present study, initially two fractions designated REC-1001 (flavonoid-rich fraction) and REC-1002 (flavonoid-poor fraction) of Hippophae rhamnoides were screened on the basis of their reducing power in the aqueous phase. REC-1001 was selected for further study, since it exhibited 27.38 times higher antioxidant activity than REC-1002. REC-1001 also showed significant (P < .05) membrane protection potential at 50 microg/mL, which was attributed to its ability to scavenge peroxyl radicals (64.82 +/- 1.25% scavenging within 1,440 min). A significant (P < .05) difference of 67.02% in free radical scavenging activity at 1,000 ng/mL between REC-1001 and vitamin E demonstrated the extract fraction's worth in radiation protection. Such activities were attributed to the presence of quercetin, isorhamnetin, and kaempferol in this fraction. Further, REC-1001 was found to be nontoxic up to 200 mg/kg of body weight. This research suggests that the REC-1001 fraction of H. rhamnoides extract is a safe and effective antioxidant nutraceutical product.

Impaired lipid metabolism resulting from uncontrolled hyperglycaemia has been implicated in cardiovascular complications in diabetes patients. The aim of this study was to examine the impact of glycaemic control on the lipid profile of diabetic patients. We also determined the ability of glycated haemoglobin (HbA(1c)) as an indirect marker of dyslipidaemia. A total of 1011 type 2 diabetic patients (males, 574; females, 437; mean age, 59.76 years) were included in this study. Venous blood samples were collected from all the subjects after at least 8 h fasting. The sera were analysed for HbA(1c), fasting blood glucose (FBG), total cholesterol, triglycerides (TG), high-density lipoprotein cholesterol (HDL) and low-density lipoprotein cholesterol (LDL). The levels of HbA(1c), FBG and LDL did not differ significantly between males and females. Female patients showed significantly higher serum cholesterol and HDL but significantly lower TG levels as compared to males. There was a highly significant correlation between HbA(1c) and FBG. Both HbA(1c) and FBG exhibited direct correlations with cholesterol, TG and LDL and inverse correlation with HDL; the magnitude of significance for all these lipid parameters being greater with HbA(1c) than FBG. There was a linear relationship between HbA(1c) and dyslipidaemia. The levels of serum cholesterol and TG were significantly higher and of HDL significantly lower in patients with worse glycaemic control as compared to patients with good glycaemic control. The findings of this study clearly indicate that HbA(1c) is not only a useful biomarker of long-term glycaemic control but also a good predictor of lipid profile. Thus, monitoring of glycaemic control using HbA(1c) could have additional benefits of identifying diabetic patients who are at a greater risk of cardiovascular complications.

This study reports the utilization of serum fructosamine and blood glucose for the screening of gestational diabetes mellitus (GDM). Blood samples from 165 pregnant women were analyzed for fasting blood glucose (FBG), random blood glucose (RBG) and serum fructosamine. The actual fructosamine levels were corrected for serum protein (c-Fruct) for more precise presentation. Two cut-off values of FBG (>5.3 mmol/L and >7.0 mmol/L) and RBG (>7.8 mmol/L and >11.0 mmol/L) were used to classify hyperglycemic subjects for subsequent evaluation. The average values±standard deviations for FBG, RBG and cFruct were 5.865±1.95, 7.767±3.21 and 2.387±0.47 mmol/L, respectively. FBG levels were significantly correlated with RBG (Pearson correlation=0.597, P<0.001). Significant correlations were also observed between cFruct and FBG (Pearson correlation=0.673, P<0.001) or RBG (Pearson correlation=0.641, P<0.001). Out of 165 subjects, 24 (14.5%) cases were classified as hyperglycemic on the basis of FBG>7.0 mmol/L or RBG>11.0 mmol/L; use of lower cut-off values resulted higher frequencies of hyperglycemia. Whereas, a combined criteria of FBG>5.3 mmol/L and cFruct >2.5 mmol/L predicted 35 patients as the most probable hyperglycemic as compared to 32 patients identified using the criteria of RBG >7.8 mmol/L and cFruct >2.5 mmol/L. These criteria were associated with 4.8% and 3.6% false-positivity at the expense of 3.6% and 3.0% false-negative outcomes, respectively. The levels of FBG, RBG and cFruct were significantly higher in hyperglycemic groups (irrespective of grouping criteria) as compared to the respective normal groups. In conclusion, these findings clearly indicate that the paired values of cFruct with FBG or RBG could help in filtering high-risk individuals for OGTT and therefore avoiding a unnecessary OGTT.

Occupational and environmental exposure of synthetic nitriles is of potential relevance to human health. Iminodipropionitrile (IDPN), a prototype nitrile toxin, has been shown to produce dyskinetic syndrome in rodents. This study reports the effect of concomitant exposure of rats to hydrocortisone and IDPN on behavioural abnormalities namely excitation, circling and chorea (ECC) syndrome. Four groups of female Wistar rats were given hydrocortisone (0, 10, 30 and 60 mg/kg, gavage, for 10 days) 30 min. before IDPN (100 mg/kg, intraperitoneally for 8 days). Two additional groups of rats were treated with either saline (control group) or 60 mg/kg of hydrocortisone (drug alone group). The animals were observed for neurobehavioural abnormalities including dyskinetic head movement, circling, tail hanging, air righting reflex and contact inhibition of righting reflex. After behavioural studies, the animals were killed, and the discrete brain regions and temporal bones were collected for biochemistry and inner ear histopathology, respectively. Hydrocortisone significantly and dose dependently attenuated the incidence and severity of IDPN-induced behavioural syndrome. Administration of hydrocortisone (60 mg/kg) alone significantly increased glutathione (GSH) levels in olfactory bulb and striatum, whereas IDPN alone significantly reduced GSH levels in olfactory bulb, striatum and hippocampus. Hydrocortisone (60 mg/kg) significantly compensated IDPN-induced depletions of GSH in different brain regions. Hydrocortisone also protected the animals against IDPN-induced vestibular hair cell degeneration. The protective effect of hydrocortisone may be attributed to its anti-inflammatory and antioxidant properties.

Surgical removal of impacted third molars is the most commonly performed procedure by oral and maxillofacial surgeons. The removal of diseased or symptomatic third molars has not been an issue of controversy. The risk of surgery and associated complications are justified and uniformly accepted by most surgeons when the teeth are associated with chronic or acute pathologic processes, including caries, nonrestorable teeth, fractured roots, resorption, associated pathologic conditions (cysts, tumors), periapical abscesses, odontogenic infections, osteomyelitis, removal before reconstructive or ablative surgery, and radiation therapy.

Both pregnancy and cyclosporin A (CsA) are known to inhibit T-cell mediated immune response and to activate phagocytes against microbial infections as a compensatory mechanism. Pregnant women, either with organ transplantation or suffering from autoimmune diseases, are commonly managed with CsA therapy. This investigation was aimed to study effect of CsA on phagocytic activity of whole blood polymorphonuclear leukocytes (PMNs) in pregnant rats. Both pregnant and non-pregnant Sprague-Dawley rats (4 animals per group) were treated with CsA (40 mg/kg, oral) for 7 days starting from gestation day 7. Respective control groups of non-pregnant and pregnant rats received vehicle only. Luminol-dependent chemiluminescence (CL) was used to measure the generation of reactive oxygen species (ROS) in respiratory burst of whole blood PMNs stimulated by zymosan. The results showed a moderate and insignificant increase in CL response in non-pregnant rats with CsA treatment or pregnant rats without CsA treatment. Whereas the CL response of whole blood PMNs was significantly higher (ANOVA F = 35.66, P < 0.001) in pregnant rats treated with CsA. In conclusion, this preliminary study demonstrates synergistic effects of pregnancy and CsA on activation of PMNs resulting in massive and sustained generation of ROS that could be deleterious to both host and fetus.

A case is presented where the common insertion of the upper and lower canaliculus of the lacrimal sac was repaired using endoscopic dacrocystorhinostomy (DCR) techniques, with silicone stenting and securing of stents intranasally.

We have evaluated the effect of variation in aryl-tetralin lignans on the radioprotective properties of Podophyllum hexandrum. Two fractionated fractions of P. hexandrum [methanolic (S1) and chloroform fractions (S2)], with varying aryl-tetralin lignan content were utilized for the present study. The peroxyl ion scavenging potentials of S1 and S2 were found to be comparable [i.e. 45.88% (S1) and 41% (S2)] after a 48 h interval in a time-dependent study, whereas in a 2 h study, S2 exhibited significant (P < 0.05) antioxidant activity in different metal ion + flux states. In the aqueous phase, S2 exhibited non-site-specific reactive oxygen species scavenging activity, i.e. 73.12% inhibition at 500 mug ml(-1). S1 exhibited 58.40 +/- 0.8% inhibition (at 0.025 mug ml(-1)) of the formation of reactive nitrite radicals, comparable to S2 (52.45 +/- 0.825%), and also showed 45.01% site-specific activity (1000 mug ml(-1)), along with significant (P < 0.05) electron donation potential (50-2000 mug ml(-1)) compared to S2. Such activities of S1 could be attributed to the significantly (P < 0.05) higher levels of podophyllotoxin beta-d-glucopyranoside (16.5 times) and demethyl podophyllotoxin glucoside (2.9 times) compared with S2. Together, these findings clearly prove that aryl-tetralin lignan content influences the radiation protective potential of the Podophyllum fractions to a great extent.

Fasting blood glucose (FBG) and serum fructosamine are simple and commonly used tests for monitoring diabetes mellitus. Unfortunately, both these parameters are associated with high error rates and therefore used with caution in high-risk populations. Setting high cut-off values for these parameters increases the sensitivity but at the cost of poor specificity (more false positives). Continued efforts have been made to evaluate the efficacy of FBG and fructosamine, singly or in combination, in avoiding a large number of unnecessary oral glucose tolerance tests (OGTT). Therefore, to better understand their time-course trends, we analysed FBG and c-fructosamine in 211 blood samples from 51 Saudi pregnant women during their multiple (> or =3) antenatal visits. The mean+/-standard deviation of FBG and c-fructosamine were 5.22+/-1.07 and 2.22+/-0.25 mmol/l respectively with a significant correlation between their individual values. Using the FBG cut-off >5.3 mmol/l, 19 subjects were classified as hyperglycaemic; this frequency was reduced to 1 when a FBG cut-off of >7.0 mmol/l was used. Combined values of FBG (>5.3 mmol/l) and c-fructosamine (>2.5 mmol/l) filtered 6 high-risk subjects with a prediction of gestational diabetes mellitus (GDM). Analysis of variance revealed high within-group variance for FBG. These fluctuations were also confirmed by higher coefficient of variations (CVs) for FBG (13.27%) as compared to c-fructosamine (5.49%). The CVs of FBG were not correlated with those of corresponding CVs of c-fructosamine (R = 0.007, P = 0.962), indicating that the fluctuations in FBG were independent of fluctuations in c-fructosamine. These findings clearly suggest that the paired values of FBG and c-fructosamine would be more advantageous than their individual values in filtering high-risk patients on whom OGTT should be performed.

Aim: To study the effect of bromophenacyl bromide (BPB), a phospholipase A2 inhibitor on gastric secretion and to protect chemically induced gastric and duodenal ulcers in rats., Methods: Acid secretion studies were undertaken in pylorus-ligated rats with BPB treatment (0, 5, 15 and 45 mg/kg). Gastric and duodenal lesions in the rats were induced by ethanol and cysteamine respectively. The levels of gastric wall mucus, nonprotein sulfhydryls (NP-SH) and myeloperoxidase (MPO) were also measured in the glandular stomach of rats following ethanol induced gastric lesions., Results: BPB produced a dose-dependent inhibition of gastric acid secretion and acidity in rats. Pretreatment with BPB significantly attenuated the formation of ethanol induced gastric lesion. BPB also protected intestinal mucosa against cysteamine-induced duodenal ulcers. The antiulcer activity of BPB was associated with significant inhibition of ethanol-induced depletion of gastric wall mucus, NP-SH and MPO. These findings pointed towards the mediation of sulfhydryls in BPB induced gastrointestinal cytoprotection., Conclusion: BPB possesses significant antiulcer and cytoprotective activity against experimentally induced gastroduodenal lesions.

Stabilization of mast cells plays a key mechanism to protect gastrointestinal tract from injury. This study presents a comparative evaluation of mast cell stabilizers nedocromil sodium (NDS) and sodium cromoglycate (SCG) in experimental gastric and duodenal ulcers in rats. Wistar rats of either sex were used in this study. Both NDS and SCG, in the doses of 10, 30 and 100 mg/kg were given intraperitoneally for gastric secretion studies and by gavage for antiulcer studies. Acid secretion studies were undertaken in pylorus-ligated rats. Gastric lesions were induced by water immersion restraint stress (WIRS), indomethacin and ethanol whereas duodenal ulcers were produced by cysteamine. The level of glutathione (GSH) and gastric wall mucus were measured in glandular stomach of rats following ethanol-induced gastric lesions. SCG was more effective than NDS in preventing WIRS- and indomethacin-induced gastric lesions whereas reverse was true in ethanol- and cysteamine-induced ulcers. All the 3 doses of SCG offered almost equal protection against WIRS-induced gastric lesions whereas only medium and high dose of NDS provided significant protection in this model of ulcer. NDS significantly inhibited cysteamine-induced duodenal ulcers whereas SCG failed to do so. Pretreatment with NDS or SCG significantly and dose-dependently protected gastric mucosa against ethanol-induced injury, while the former drug appeared to be more effective. The cytoprotective effects of these two drugs were accompanied by the attenuation of ethanol-induced depletion of gastric wall mucus and GSH. The differential effects of NDS and SCG against various gastric lesions rationalize the possible benefits of a combined therapy (NDS+SCG) for the treatment of complex gastroduodenal ulcers.

Survival curves are frequently used for reporting survival or mortality outcomes of experimental pharmacological/toxicological studies and of clinical trials. Microsoft Excel is a simple and widely used tool for creation of numerous types of graphic presentations however it is difficult to create step-wise survival curves in Excel. Considering the familiarity of clinicians and biomedical scientists with Excel, an algorithm survival curves in Excel worksheet (SCEW) has been developed for easy creation of survival curves directly in Excel worksheets. The algorithm has been integrated in the form of Excel add-in for easy installation and usage. The program is based on modification of frequency data for binary break-up using the spreadsheet formula functions whereas a macro subroutine automates the creation of survival curves. The advantages of this program are simple data input, minimal procedural steps and the creation of survival curves in the familiar confines of Excel.

A semi-purified extract of low-altitude Podophyllum hexandrum (REC-2001) containing a relatively low content of podophyllotoxin (3.25 %) exhibited potent antioxidant ability in lipid media (at 1000 microg/mLagainst 0.25 kGy) and significant (p < 0.05) hydroxyl ion scavenging potential (78.83 % at 500 microg/mL). In vitro investigations revealed the ability of REC-2001 to significantly (p < 0.05) reduce radiation-induced hemolysis (2 microg/mL; 46.184 %) and nitric oxide scavenging levels (IC (50): 792 +/- 1.25 microg/mL). Protection of the hemopoietic system of Strain 'A' mice administered 20 mg/kg BW REC-2001 30 min prior to lethal irradiation (10 Gy) was recorded and was mediated by free radical scavenging and lowering of lipid oxidation. Further studies investigating the effects of REC-2001 on stem cell modulation are warranted.

This study examined the effect of Echis pyramidum (EP) venom on time-course of lipid peroxidation in different vital organs of mice. Adult male Swiss albino mice were injected with EP venom (2 mg/kg, i.p.); control mice received vehicle alone (normal saline). Mice were killed at 1, 3, 6, 12, and 24 h post-envenomation. The liver, lung, kidney, heart, and brain (cerebrum and cerebellum) were collected for the estimation of malondialdehyde (MDA), an index of lipid peroxidation. The results of this study showed that a single injection of EP venom caused a significant lipid peroxidation in all the organs studied. The onset of lipid peroxidation was as early as 1 h and persisted for several hours, suggesting an important role of oxidative stress in the cytotoxicity of EP venom., ((c) 2006 Wiley Periodicals, Inc.)

The modulatory effect of cadmium pretreatment (0.2 mg/kg b.w. i.p.) on deltamethrin-induced oxidative stress and alterations of antioxidants was studied in freshwater fish Channa punctata Bloch. Lipid peroxidation (LPO) was measured as one of the indicators of oxidative stress. Activities of glutathione peroxidase, glutathione reductase, and glutathione-S-transferase were also studied in liver, kidney, and gills. Levels of reduced glutathione (GSH) were measured in various tissues. Fish pretreated with cadmium and subsequently exposed to deltamethrin showed significantly reduced LPO values when compared with deltamethrin-exposed fish. Conversely, in the kidney, a potentiation response was observed. Deltamethrin exposure in fish resulted in significant alteration in activities of glutathione-dependent antioxidant enzymes. In the cadmium preexposed fish, which were subsequently exposed to deltamethrin, antioxidant enzymes showed a tendency toward normalization over deltamethrin-only exposed fish in liver and gills. GSH also showed a similar pattern in liver and gills but in kidney it remained elevated. Cadmium alone had no significant effect on various parameters at the concentration used in this study. When metallothionein (MT) induction was studied, only liver showed an MT-like protein band in sodium dodecylsulfate-polyacrylamide gel electrophoresis analysis. These results demonstrate a modulatory role of cadmium on the oxidative stress and other related parameters in liver and gills. These findings are important in the context of exposure to a mixture of pollutants in aquatic environment.

Nicotinic acetylcholine receptors (nAChRs) are regarded as potential therapeutic targets to control various neurodegenerative diseases. Owing to the relevance of cholinergic neurotransmission in the pathogenesis of Huntington's disease (HD) this investigation was aimed to study the effect of nicotine, a nAChR agonist, on 3-nitropropionic acid (3-NP)-induced neurodegeneration in female Wistar rats. Systemic administration of 3-NP in rats serves as an important model of HD. The animals received subcutaneous injections of nicotine (0, 0.25, 0.50 and 1.00 mg/kg) daily for 7 days. 3-NP (25 mg/kg, i.p.) was administered daily 30 min after nicotine for the same duration. One additional group of rats served as control (vehicle only). On day 8, the animals were observed for neurobehavioral performance (motor activity, inclined plane test, grip strength test, paw test and beam balance). Immediately after behavioral studies, the animals were transcardially perfused with neutral buffered formalin (10%) and brains were fixed for histological studies. Lesions in the striatal dopaminergic neurons were assessed by immunohistochemical method using tyrosine hydroxylase (TH) immunostaining. Treatment of rats with nicotine significantly and dose-dependently attenuated 3-NP-induced behavioral deficits. Administration of 3-NP alone caused significant depletion of striatal dopamine (DA) and glutathione (GSH), which was significantly and dose-dependently attenuated by nicotine. Preservation of striatal dopaminergic neurons by nicotine was also confirmed by immunohistochemical studies. These results clearly showed neuroprotective effect of nicotine in experimental model of HD. The clinical relevance of these findings in HD patients remains unclear and warrants further studies.

The aqueous-ethanolic extract (AEE) of high altitude Podophyllum hexandrum has earlier been reported to render a radioprotective effect against lethal gamma radiation in in vitro model. AEE has also been reported to possess metal chelating and DNA protecting properties. The present study was undertaken to isolate and characterize the bioactive principle present in AEE and investigate its role in radiation protection. A novel molecule was found to be present in AEE and was assigned as 3-O-beta-D-galactoside of quercetin by acid hydrolysis, LC-MS, LC-APCI-MS/MS and 13C NMR spectra. Various biological activities were investigated at in vitro level. The antioxidant potential of AEE in lipid and aqueous phase was determined against numerous stresses. AEE was found to be significantly (p < 0.05) protective, i.e., against Fe2+ and Cu2+-induced linoleic acid degradation, respectively. Radiation-induced lipid oxidation studies revealed that AEE maximally works at a [lignan]/0.25 kGy ratio 400 (ratio of concentration of AEE divided by the radiation dose, i.e., 0.25 kGy) and no drug-induced lipid oxidation at all concentrations tested was found. In a time-dependent study, total antioxidant activity was maximally exhibited at 1 mg/ml. The site-specific and non-site-specific deoxyribose degradation assay exhibited a dose-dependant hydroxyl scavenging potential of AEE (0.05-500 microg/ml). The anti-lipid peroxidation ability of AEE against radiation (0.25 kGy)-induced lipid peroxidation was higher in case of neural tissue homogenate as compared to kidney homogenate [activity ratio: 0.039 (brain) < 0.24 (kidney)]. The protein protection study using bovine serum albumin was also done for two time intervals (2 h and 4 h) and significant (p < 0.05) protection was observed at 500 microg/ml (> 97%). This study implies that 3-O-beta-D-galactoside present in AEE renders radioprotection by protecting lipids, proteins in renal and neural model system against supra-lethal (0.25 kGy) gamma radiation.

Alanine at residue 73 (Ala-73) and aspartate at residue 9 (Asp-9) are characteristic to both Cw6 and Cw7 alleles of HLA-C gene and have been suggested as possible markers for psoriasis vulgaris (PsV). However, the results from various ethnic groups/populations are contradictory and inconclusive. In this study, an attempt has been made to examine the association between HLA-C (Ala-73 and Asp-9) and susceptibility to PsV among Saudi patients. Genomic DNA was extracted from 25 Saudi PsV patients and 75 control subjects. Polymerase chain reaction (PCR) was performed to amplify HLA-C sequences using earlier reported primers, C133P and C243PR. Sequence-specific primers were used to specifically detect nucleotide coding for Ala-73 and Asp-9 in all the subjects. The results showed significantly higher frequency of Asp-9 (84.0 % versus 61.3 %) in PsV patients as compared to controls (p < 0.05, 2-tailed Fisher's exact test). The frequencies of Ala-73 among PsV patients (92 %) and controls (88 %) did not differ significantly.

Recently, fluconazole (FLZ) has been shown to improve survival and reduce multiorgan failure in experimental and clinical septic shock. The mechanism by which FLZ affords protection against sepsis remains obscure. This study examines the effect of FLZ on phagocytic activity of polymorphonuclear leukocytes (PMNs) in a rat model of septic shock by inducing fecal peritonitis in male Wistar rats using intraperitoneal instillation (1 mL/kg) of fecal suspension in saline (1:1 w/v). Sham control rats received sterile fecal suspension and vehicle treatment. FLZ was administered in the doses of 0, 3, 10, and 30 mg/kg by gavage 30 minutes before fecal instillation. The samples of peritoneal fluid were collected 8 hours following fecal inoculation for the evaluation of phagocytic response of PMNs using zymosan-induced luminol-dependent chemiluminescence (CL). Fecal peritonitis caused massive infiltration of PMNs in the peritoneal cavity (ANOVA F(4,45) = 6.322, P < .001). Although FLZ reduced the infiltration of PMNs, this effect was neither significant nor dose dependent. The actual CL response was significantly higher in the peritoneal fluid of rats subjected to peritonitis, which was significantly and dose dependently attenuated by FLZ treatment (ANOVA F(4,45) = 11.048, P < .001). Normalization of CL response for 1000 PMNs revealed that FLZ dose-dependently albeit insignificantly reduced the activity of PMNs. The high dose of FLZ caused 2.29-fold decrement in the area under curve (AUC) pertaining to cumulative CL response. The findings of this study suggest that FLZ protects rats against septic shock by inhibiting PMN-mediated inflammatory cascade without compromising their phagocytic activity.

Due to versatile diagnostic and prognostic fidelity molecular signatures or fingerprints are anticipated as the most powerful tools for cancer management in the near future. Notwithstanding the experimental advancements in microarray technology, methods for analyzing either whole arrays or gene signatures have not been firmly established. Recently, an algorithm, ArraySolver has been reported by Khan for two-group comparison of microarray gene expression data using two-tailed Wilcoxon signed-rank test. Most of the molecular signatures are composed of two sets of genes (hybrid signatures) wherein up-regulation of one set and down-regulation of the other set collectively define the purpose of a gene signature. Since the direction of a selected gene's expression (positive or negative) with respect to a particular disease condition is known, application of one-tailed statistics could be a more relevant choice. A novel method, ArrayVigil, is described for comparing hybrid signatures using segregated-one-tailed (SOT) Wilcoxon signed-rank test and the results compared with integrated-two-tailed (ITT) procedures (SPSS and ArraySolver). ArrayVigil resulted in lower P values than those obtained from ITT statistics while comparing real data from four signatures.

We investigated the mobility of DNA fragments labeled with the fluorescent dyes R110 and R6G, specifically for use in genotyping using capillary electrophoresis. Genomic DNA was isolated from blood, and a highly polymorphic region of the HLA-C gene was amplified by PCR with the use of either [F]-dNTP-[R110] or [F]-dNTP-[R6G]. Pre-diluted (30-fold) PCR products were mixed with formamide, denatured (at 95 degrees C for 2 min.), and rapidly cooled on ice before being subjected to electrophoresis. The results showed that the number and mobility of allele-specific DNA fragments were independent of the two dyes used. Both dyes were equally efficient at differentiating homozygous or heterozygous allelic presentation. An additional dye-specific peak of 132-base-pair mobility was observed with the use of [F]-dNTP-[R110]; it significantly impaired the resolution of one allele-specific peak. The electropherograms obtained with [F]-dNTP-[R6G] were free from any interfering peaks within the target region, thus the [R6G]-based procedure is more preferable for genotype analysis. As this procedure does not involve any post-PCR cleanup, it is simple, rapid and cost-effective.

This study reports the effects of the antioxidant sodium benzoate (SB) on iminodipropionitrile (IDPN)-induced excitation with choreiform and circling (ECC) syndrome in adult female Wistar rats. Rats in four different groups (n=8) received i.p. injections of SB (0, 50, 100 and 200 mg/kg) daily for 10 days. IDPN (100 mg/kg, i.p.) was administered daily 30 min before SB for the first 8 days. Two additional groups served as control (vehicle) and SB alone (200 mg/kg) groups. The animals were observed daily for neurobehavioral abnormalities, including dyskinetic head movements, circling, tail hanging, righting reflex and contact inhibition of the righting reflex, characterized as the ECC syndrome. In the IDPN-alone treated group, the onset of ECC syndrome occurred on day 9 (2 out of 8 rats), whereas none of the animals treated with IDPN plus SB (100 or 200 mg/kg) showed any signs of ECC syndrome on that day. All the animals in the IDPN-alone group developed severe dyskinesia on day 11. Treatment of rats with SB significantly and dose-dependently attenuated IDPN-induced behavioral deficits.

The sensitivity of capillary electrophoresis coupled with laser-induced fluorescence (CE-LIF) was compared with conventional agarose gel electrophoresis-ethidium bromide-UV method (AE-EUV) for detection and semi-quantitative determination of GFAP mRNA in mouse brain. GFAP expression was induced by the neurotoxin MPTP in C57BL mice. Serially diluted RNA samples (0.0003, 0.003, 0.03, 0.3, and 3 microg total RNA) were subjected to RT-PCR and analyzed by both procedures. The integrated pixel density (AE-EUV) and peak area (CE-LIF) were directly proportional to the amount of RNA. However, the observed high sensitivity of CE-LIF suggests its potential application for detection and semi-quantitative determination of low-abundance mRNA transcripts.

Several buffer compositions with a wide range of pH values have been reported for radiometric assay of tyrosine hydroxylase (TH) in biological samples. Assay sensitivity becomes a prime concern while analyzing TH in minute samples like tissue biopsies or discrete regions of rodent brain wherein lower enzyme levels are anticipated due to smaller sample sizes. It was therefore rationalized to evaluate relative affinities of three commonly used assay buffers (sodium phosphate, sodium acetate, and Tris-acetate) with TH enzyme activity. The impact of buffer pH and cofactor concentration on the sensitivity of TH assay was also investigated. Striata from rats or mice were homogenized, respectively, with 1.0 or 0.5 ml of the assay buffer containing 0.5% Triton X-100. The supernatants (200 microl) were incubated (20 min, 37 degrees C) with 0.8 microCi [3H] L-tyrosine, 1.5 mM DL-6-methyl-5,6,7,8-tetrahydropterine (6-MPH4), 100 U catalase, and 1.0 microM dithiothreitol in a total volume of 300 microl. The reaction was terminated by 1-ml suspension of activated charcoal in 0.1 M HCl. After centrifugation, 200-microl aliquots were mixed with 5 ml of cocktail for quantitation of [3H] H2O in supernatant. The results showed significant impact of pH rather than the buffer composition on the sensitivity of TH assay. An optimal pH range was found to be 5.5-6.0, whereas TH activity was significantly inhibited at pH 5.0 and pH 6.8 (F = 55.09, P = 0.000). A significantly high TH activity was observed with 1.5 mM 6-MPH4, whereas higher concentrations (3.0-4.5 mM) inhibited TH activity (F = 7.47, P = 0.005). Analysis of serially diluted striatal homogenates showed a significant correlation between TH activity and sample amount. The assay reaction was linear for 20- and 30-min incubation for rat and mice striata, respectively.

Few techniques are described specifically for reconstruction of full thickness defects involving the chin. We present a new method of reconstruction of a large full thickness defect over the chin and lower labial sulcus with four V-Y island flaps. Two of these were mental neurovascular island flaps. The other two were islanded musculomucosal flap. The mental flaps, previously described for reconstruction of the lower lip, were cosmetically more suitable for reconstruction of tissue defects of the chin. The principle of covering the tissue defect of chin with local tissue to provide good matching and function is achieved.

This study examines a concurrent profiling of circulating and extravasated polymorphonuclear leukocytes (PMNs) in a rat model of experimental sepsis. Fecal peritonitis was induced in Wistar male rats by intraperitoneal instillation of a fecal suspension in saline (1:1 w/v). Blood and peritoneal fluid were collected 8 h following fecal inoculation for the evaluation of inflammatory response of PMNs using zymosan-induced luminol-dependent chemiluminescence. Fifty microliters of pre-diluted blood or peritoneal fluid samples were mixed with 150 microl of reaction mixture (4 x 10(-4) M luminol+50 microg opsonized zymosan+0.1% gelatin in Hank's balanced salt solution) and the chemiluminescence signal was measured in a luminometer at 37 degrees C. Fecal peritonitis caused a significant leukocytopenia (3540+/-297 mm(-3) versus control value of 7525+/-711 mm(-3), p < 0.001) accompanied by massive infiltration of PMNs in the peritoneal cavity (34700+/-4006 versus 7325+/-425 mm(-3), p < 0.001). The phagocytic activity of circulating blood PMNs was down-regulated whereas a significant up-regulation was observed in the activity of PMNs from peritoneal fluid. In conclusion, this study clearly demonstrates sepsis-induced alterations in both blood and peritoneal fluid PMNs and their quantitative assessment may be helpful in disease evaluation and designing effective therapies.

Introduction: Photography is commonly used to evaluate macroscopic morphology of experimental gastric lesions. The conventional methods for quantitation of these lesions tend to be highly subjective, error-prone, and tedious. This study reports a simple and novel method for visualization of experimental gastric lesions by direct scanning of stomach samples and their quantitation by using computer-assisted image analysis., Methods: Gastric mucosal lesions were produced by indomethacin or ethanol in male Wistar rats. The stomachs were removed, opened along the greater curvature, and washed. The flattened stomach samples were sandwiched within a transparent plastic folder and scanned. The captured image was saved and subjected to lesion quantitation using a freely accessible image analysis program, Scion Image. A macro subroutine was optimized for automation of the entire procedure for ease in frequent applications., Results: The images obtained by direct scanning of stomach samples showed excellent morphologic visualization of gastric lesions. The standard spots having variable areas of same density, or same areas of variable densities, showed a direct relation with signal intensity (pixels). A linear correlation was observed between measured and actual values of the known standard areas. The representative samples of indomethacin- and ethanol-induced gastric ulcers showed the total lesion areas of 4.62+/-0.74 and 169.26+/-13.23 mm(2), respectively., Discussion: Direct scanning of stomach samples is a simple, cost-effective, rapid, and efficient procedure for morphologic evaluation of experimental gastric lesions. The output images of scanned stomach samples are superior to scanned photographs, and can be instantly used for quantitative assessment of mucosal injury using the image analysis program.

Immunological abnormalities have been described in idiopathic Parkinson's disease and in the mouse model of this disorder induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). This investigation was aimed to study the effect of MPTP on inflammatory response of whole blood phagocytes at different time intervals. C57BL male mice were injected intraperitoneally with either MPTP (30 mg/kg) or saline (control group) and the blood samples were collected at 4, 24 and 48 h. 50 microl of a 500-fold diluted blood sample was mixed with 150 microl of reaction mixture (0.4 mM luminol + 50 microg opsonized zymosan + 0.1% gelatin, in Hanks' balanced salt solution) and the chemiluminescence (CL) signal was measured in a luminometer at 37 degrees C. Although the CL response of the whole blood from control and MPTP groups was similar at 4 h, a significant increase in the CL signal was observed in MPTP-treated mice at 24 h post-treatment, which got subsided at 48 h. The findings of this study suggest that in an early stage a pro-inflammatory response following MPTP might trigger a chain of potentially toxic pathways mediated by reactive oxygen species, leading to progressive neuronal damage.

The massive surge in the production of microarray data poses a great challenge for proper analysis and interpretation. In recent years numerous computational tools have been developed to extract meaningful interpretation of microarray gene expression data. However, a convenient tool for two-groups comparison of microarray data is still lacking and users have to rely on commercial statistical packages that might be costly and require special skills, in addition to extra time and effort for transferring data from one platform to other. Various statistical methods, including the t-test, analysis of variance, Pearson test and Mann-Whitney U test, have been reported for comparing microarray data, whereas the utilization of the Wilcoxon signed-rank test, which is an appropriate test for two-groups comparison of gene expression data, has largely been neglected in microarray studies. The aim of this investigation was to build an integrated tool, ArraySolver, for colour-coded graphical display and comparison of gene expression data using the Wilcoxon signed-rank test. The results of software validation showed similar outputs with ArraySolver and SPSS for large datasets. Whereas the former program appeared to be more accurate for 25 or fewer pairs (n < or = 25), suggesting its potential application in analysing molecular signatures that usually contain small numbers of genes. The main advantages of ArraySolver are easy data selection, convenient report format, accurate statistics and the familiar Excel platform.

Objective: Acute lung injury following peritonitis constitutes an enigmatic clinical problem with no specific therapy. Recently, immunomodulators such as azole compounds have been shown to attenuate shock-related tissue injury. The present investigation was undertaken to study the effect of fluconazole on acute lung injury and survival following faecal peritonitis in rats., Subjects: Male Wistar rats weighing 225-235 g., Design and Setting: Faecal peritonitis (Fp) was produced in four groups of adult male Wistar rats by intraperitoneal administration of non-sterile faecal suspension (1:1 w/v saline). A fifth group of rats was given sterile faecal material (SFM), which served as control., Interventions: Rats in Fp groups were given fluconazole in doses of 0 mg/kg, 3 mg/kg, 10 mg/kg, and 30 mg/kg by gavage 30 min before induction of peritonitis. The control animals received an equal volume of distilled water., Measurements and Results: Survival over a period of 72 h, oxidative stress, neutrophil activity, and lung injury were measured. This study showed a 90% survival in the fluconazole-treated group compared to only 20% survival in untreated rats (P<0.008 log-rank test). The lungs of animals with Fp showed massive pathological changes including intraalveolar oedema, fibrosis, and mixed inflammatory cell infiltrate. These changes were dose-dependently attenuated by fluconazole. Enhanced oxidative stress (P<0.001) and neutrophil activity in the peritoneal fluid and lung (P<0.001) in Fp animals was dose-dependently reduced by fluconazole., Conclusion: This study clearly suggests the role of neutrophils in Fp-induced tissue injury/mortality, which may be dose-dependently, attenuated by fluconazole.

A direct association between aging and drug-induced dyskinesia has been reported by several investigators. Iminiodipropionitrile (IDPN), a prototype nitrile compound produces a motor syndrome in rodents, which resembles neuroleptic drug induced dyskinesia. In this investigation attempt has been made to study the effect of age on IDPN induced vestibular hair cell degeneration and resulting dyskinetic syndrome. Male Wistar rats aged 3, 6 and 12 weeks received IDPN in the doses of 0, 200 and 400 mg/kg, intraperitoneally for 3 consecutive days. IDPN-induced dyskinesia was assessed using a behavioral testing battery on days 3, 4, 5, 6, 7, 14, 21 and 28. The rats were sacrificed on day 28; temporal bones were excised for vestibular histopathology and sera were collected for measuring the indices of oxidative stress (glutathione and conjugated dienes). IDPN in the dose of 200 mg/kg produced dyskinesia in 12 weeks old rats, but failed to do so in 3 and 6 weeks old rats. The high dose of IDPN (400 mg/kg) caused dyskinesia in all age groups, however, its onset and severity were age-dependent. Older rats showed an early onset and significantly high incidence of dyskinesia as compared to younger rats. The susceptibility of rats to IDPN-induced behavioral deficits was proportional to oxidative stress and degeneration of sensory hair cells in the crista ampullaris.

Firefly luciferase bioluminescence (FLB) is a highly sensitive and specific method for the analysis of adenosine-5-triphosphate (ATP) in biological samples. Earlier attempts to modify the FLB test for enhanced sensitivity have been typically based on in vitro cell systems. This study reports an optimized FLB procedure for the analysis of ATP in small tissue samples. The results showed that the sensitivity of the FLB test can be enhanced several fold by using ultraturax homogenizer, perchloric acid extraction, neutralization of acid extract and its optimal dilution, before performing the assay reaction.

This Visual Basic computer program has been developed for drug dosage conversions using metabolically active mass (MAM) of the animals. The two body weights (one with known dosage and the other, for which the dosage has to be calculated) and the known dosage are entered in the respective input boxes and the appropriate units are selected using the option buttons. The program displays the report in the form of both the animals' body weights and the respective dosages in milligram per kilogram body weight as well as the total actual doses in milligrams. The object oriented layout, flexible data entry and comprehensive report format render the CalcDose software a convenient and handy tool for dosage conversions.

Iminodipropionitrile (IDPN) produces irreversible behavioral abnormalities characterized by excitation with choreiform and circling movements (ECC) syndrome in rodents. Concomitant exposure to drugs or environmental chemicals has been shown to alter IDPN-induced neurobehavioral toxicity. This investigation was undertaken to study the effect of sodium salicylate (SS) on IDPN-induced behavioral abnormalities in rats. The animals were exposed to IDPN (100 mg/kg ip) daily for 8 days. SS was administered daily 30 min before IDPN in the doses of 50, 100 and 200 mg/kg ip for 12 days. The animals were observed for neurobehavioral abnormalities including dyskinetic head movements, circling, tail hanging, air righting reflex and contact inhibition of the righting reflex. Horizontal and vertical locomotor activities and forelimbs grip strength were also measured. After behavioral studies, the animals were sacrificed, and the cerebrum and temporal bones were collected for glutathione analysis and inner ear histopathology, respectively. The onset of ECC syndrome was observed on Day 9 in the IDPN-alone group with 100% incidence on Day 12. Cotreatment with salicylate dose-dependently delayed the onset time and significantly attenuated the incidence and severity of IDPN-induced neurobehavioral signs. IDPN alone significantly increased horizontal motor activity and reduced vertical motor activity and forelimbs grip strength; these effect were significantly reversed by salicylate treatment. Treatment with salicylate also attenuated IDPN-induced depletion of GSH in the cerebrum, suggesting its free radical scavenging property.