Nephropathy in Zucker diabetic fat rat is associated with oxidative and nitrosative stress: prevention by chronic therapy with a peroxynitrite scavenger ebselen

Zucker diabetic fat (ZDF) rats with the metabolic syndrome and hyperlipidemia develop focal and segmental sclerosis. The role of oxidative and nitrosative stress in the nephropathy in ZDF was studied. Renal histology, function, and immunohistologic and biochemical parameters of oxidative and nitrosative stress were evaluated at 8 and 22 wk of age in ZDF and Zucker lean (ZL) rats and after chronic treatment with ebselen, an antioxidant and peroxinitrite scavenger. At 8 wk, ZDF rats showed hyperglycemia, no proteinuria or nephropathy, but higher levels of dihydrobiopterin and 3-nitrotyrosine (3-NT)-modified proteins compared with age-matched ZL rats. At 22 wk, ZDF rats developed focal and segmental sclerosis, proteinuria, decreased creatinine clearance, and renal tissue levels of glutathione and tetrahydrobiopterin with further elevation in dihydrobiopterin and 3-NT-modified proteins, in contrast to age-matched ZL rats. Renal immunohistologic expression of lipid peroxidation products and 3-NT-modified proteins also increased in 22-wk-old ZDF but not in ZL rats. Chronic ebselen treatment of ZDF rats restored renal tissue levels of glutathione and tetrahydrobiopterin; prevented significant accumulation of dihydrobiopterin, lipid peroxidation products, and 3-NT-modified proteins; and ameliorated focal and segmental sclerosis, proteinuria, and fall in creatinine clearance without affecting mean BP, body weight, and blood glucose, compared with the untreated ZDF rats. Chronic ebselen therapy also ameliorated vasculopathy with lipid deposits and tubulointerstitial scarring, inflammation, and upregulated alpha-smooth muscle actin expression. These findings suggest that ZDF rats develop a progressive nephropathy with glomerular, vascular, and tubulointerstitial pathology. Oxidative and nitrosative stress predates the nephropathy, which is improved by peroxinitrite scavenger ebselen, and thus considered its cause and not consequence.     

Antitussive activity of the tachykinin NK1 receptor antagonist, CP-99994, in dogs

CP-99994 [(+)-(2S,3S)-3-(2-methoxybenzylamino)-2-phenylpiperidine] is a selective tachykinin NK(1) receptor antagonist that inhibits cough in guinea pigs and cats. This study examined the antitussive effects of CP-99994 in dogs produced by mechanical stimulation of the intrathoracic trachea. CP-99994 (10 mg/kg, p.o.) inhibited cough frequency by 52% at 2 h, 31% at 6 h and by 21% at 24 h. Cough amplitude was inhibited by 45% at 6 h but unchanged at 2 and 24 h after CP-99994. Plasma levels of CP-99994 were highest at 2 h (75+/-26 ng/ml) and fell to 22+/-6 ng/ml at 6 h. These results demonstrate antitussive activity of CP-99994 in dogs at a dose proven to antagonize tachykinin NK(1) receptors in this species.     

Cutaneous reactions in patients with solitary cysticercus granuloma on phenytoin sodium

Several medical conditions are believed to be associated with an increased risk of cutaneous adverse reactions to anti-epileptic drugs. The aim of this study was to study the frequency and nature of cutaneous reactions in a cohort of patients being treated with phenytoin sodium for seizures, who were divided into those with a solitary cysticercus granuloma (SCG) and those with a condition other than SCG, to determine if the presence of SCG increases the risk of cutaneous adverse reaction to phenytoin. A cohort of 117, consecutively begun on treatment with phenytoin for seizure control, were followed up prospectively for the development of cutaneous reactions. There were 63 patients with SCG upon imaging and 54 patients to whom phenytoin was administered for seizures due to causes other than SCG or multiple neurocysticercosis. Cutaneous reactions were significantly more common (p = 0.02) in patients with SCG (9/63 patients; 14.3%) than in controls (2/54 patients; 3.7%). The spectrum of skin reactions in patients with SCG included benign skin rash (n = 3), anticonvulsant hypersensitivity syndrome (n = 4), Stevens-Johnson syndrome (n = 1), and urticaria (n = 1). Individuals with seizures due to SCG have a high incidence of cutaneous adverse reactions to phenytoin. This fact should be kept in mind when initiating them on treatment with this anti-epileptic drug.     

Protective effect of naringin, a bioflavonoid on ferric nitrilotriacetate-induced oxidative renal damage in rat kidney

An iron chelate, ferric nitrilotriacetate (Fe-NTA), induces acute proximal tubular necrosis as a consequence of lipid peroxidation and oxidative tissue damage that eventually leads to high incidence of renal adenocarcinomas in rodents. This study was designed to investigate the effect of Naringin, a bioflavonoid with anti-oxidant potential, on Fe-NTA-induced nephrotoxicity in rats. One hour after a single intra-peritoneal (i.p.) injection of Fe-NTA (8 mg iron/kg body weight), a marked deterioration of renal architecture and renal function was observed. Fe-NTA induced a significant renal oxidative stress, demonstrated by elevated thiobarbituric acid reacting substances (TBARS) and reduction in activities of renal catalase, superoxide dismutase, and glutathione reductase. Pre-treatment of animals with Naringin, 60 min before Fe-NTA administration, markedly attenuated renal dysfunction, morphological alterations, reduced elevated TBARS, and restored the depleted renal anti-oxidant enzymes. These results clearly demonstrate the role of oxidative stress and its relation to renal dysfunction and suggest a protective effect of Naringin on Fe-NTA-induced nephrotoxicity in rats.     

Heterotopic pregnancy: successful management with aspiration of cornual/interstitial gestational sac and instillation of small dose of methotrexate

OBJECTIVES: Terminating a corneal pregnancy without jeopardizing a coexistent intrauterine pregnancy. METHODS: A 29-year-old woman with a 4-year history of primary infertility became pregnant after in-vitro fertilization and embryo transfer. A heterotopic pregnancy with a left cornual and intrauterine sacs was confirmed by early transvaginal scan examinations. The ectopic sac was aspirated under ultrasound guidance followed by local injection of 12.5 mg methotrexate. This was followed by serial ultrasound scans and serum betahCG assays. RESULTS: The fetal pole in the ectopic pregnancy disappeared following the procedure. She had no significant vaginal bleeding or any other unusual symptoms. The intrauterine pregnancy progressed satisfactorily until spontaneous onset of labour and vacuum extraction delivery at 39 weeks. The baby weighed 2.9 kg. CONCLUSIONS: Local injection of low-dose methotrexate following aspiration of a cornual pregnancy proved effective in halting the ectopic trophoblasts' growth without adversely affecting a coexistent intrauterine pregnancy. The injected ectopic trophoblasts resolved quickly despite the small dose of methotrexate used. This technique avoided a more costly surgical treatment with its associated risks in subsequent pregnancies.     

Co-occurring psychiatric disorders in women with addictions

There is clinically important comorbidity between psychiatric and substance use disorders, particularly in women. Women with affective and anxiety disorders are more likely to present with alcohol or drug abuse/dependence. In turn, substance-abusing women are more likely to experience clinically significant depression and anxiety. Emerging evidence is pointing to an etiological role for anxiety disorders in the development of substance abuse/dependence; however, etiologic evidence is not as clear-cut for major depressive disorder. PTSD appears to be a particularly important factor for alcohol and drug dependence in women who have experienced childhood or adult sexual and or physical abuse. Although pharmacotherapy for affective or anxiety disorders is useful for ameliorating psychiatric symptoms, research is mixed on the effectiveness for improving alcohol- and drug-related outcomes. There is some limited evidence that women-specific services can improve treatment retention, substance use outcomes, and possibly psychosocial functioning compared with traditional mixed-gender programs. However, it is clear that women with co-occurring psychiatric and substance use problems are challenging to engage and retain in care. Physicians providing women's reproductive health services can serve a vital role in the identification and referral of substance-abusing women. Particular attention should be focused on screening and assessment of alcohol and drug use and problem severity among women who have identified psychiatric disorders or who are receiving antidepressant or anxiolytic medications. Recognition and referral for both psychiatric and substance use disorders are critical for long-term health and psychosocial improvement.     

Tension-free vaginal tape procedure is an ideal treatment for obese patients

OBJECTIVES: The purpose of this study was to evaluate the effect of obesity on the success of the tension-free vaginal tape (TVT) procedure for stress urinary incontinence. Specifically, do patients with a body mass index (BMI) of 35 kg/m(2) or greater have a lower cure rate of stress urinary incontinence?STUDY DESIGN: This retrospective cohort study identified 35 patient pairs who had undergone TVT in Winnipeg, Manitoba, Canada, for stress urinary incontinence from November 1999 to July 2001. Obese patients (defined as BMI greater than or equal to 35 kg/m(2)) were paired with nonobese patients (defined as BMI less than or equal to 30 kg/m(2)). The subjects were matched for age (within 5 years) and prior continence surgeries. Patients with a maximum urethral closure pressure of less than or equal to 20 cm H(2)O were excluded. Follow-up was either by objective cough stress test or subjective cure assessed by telephone interview. Cure was defined as no postoperative stress incontinence. Statistical analysis was performed by conditional logistic regression for matched controls. RESULTS: The follow-up range was 6 to 24 months. There were seven failures in all, four in obese and three in nonobese patients, giving cure rates of 88.6% and 91.4%, respectively. This difference was not statistically significant (P>.05). There were five bladder perforations (identified at the time of the procedure), all occurring in nonobese patients (P< .05). CONCLUSION: These data do not demonstrate a difference in cure of TVT in obese versus nonobese patients. Given the finding of fewer complications, this procedure may be an ideal surgical treatment modality for stress urinary incontinence in obese women.     

Carvedilol, an antihypertensive drug with antioxidant properties, protects against glycerol-induced acute renal failure

BACKGROUND/AIMS: The pathogenesis of glycerol-induced myoglobinuric acute renal failure involves, among other causes, ischaemia, vascular congestion and reactive oxygen metabolites. The aim of this study was to investigate the role of carvedilol, an antihypertensive drug with antioxidative potential, in glycerol-induced acute renal failure in rats. METHODS: Three groups of rats were employed in this study. Group 1 served as control, group 2 was given 50% glycerol (8 ml/kg, i.m.) and group 3 was given glycerol plus carvedilol (3 mg/kg, i.p.). Renal injury was assessed by measuring plasma creatinine, blood urea nitrogen, creatinine and urea clearance. The oxidative stress was measured by renal malondialdehyde levels, reduced glutathione levels and enzymatic activity of catalase, glutathione reductase and superoxide dismutase. RESULTS: Glycerol treatment resulted in marked renal oxidative stress and significantly deranged renal functions. Both of these factors were significantly improved by carvedilol treatment. Carvedilol, by its interaction with Fenton reaction chemistry and radical scavenging activity, protected the kidney against the oxidative stress and resultant renal dysfunction produced by glycerol. CONCLUSION: Based on these results, this study indicates the protective effect of carvedilol in this rhabdomyolysis-mimicking model.     

Disaster management in India: the case of livestock and poultry

Developing countries are becoming increasingly aware of the importance of disaster management systems, and increasing efforts are being made to streamline preparedness, response and recovery mechanisms at all levels. It is well known that many developing countries, including India, are not always well-prepared to deal with disasters. A lack of well-developed disaster management plans results in a severe loss of human life, animal life and property, which could be saved if the necessary mechanisms were in place. A lot needs to be done to improve the situation, particularly in regard to livestock. This paper describes in detail, with particular reference to India, what can be done to care for animals when natural disasters occur. The authors review various types of natural disasters and their impact on livestock, and outline different preparedness, response, recovery, and mitigation strategies. The roles of different agencies, including veterinarians, are also considered.