Class benefits of AT1 antagonists in Type 2 diabetes with nephropathy

Diabetes mellitus has reached epidemic proportions in many countries and is the most common cause of end stage renal disease (ESRD). The angiotensin II receptor-1 (AT1) antagonists losartan and irbesartan have recently been evaluated as renoprotective agents in large clinical trials of patients with Type 2 diabetes and nephropathy. In the Reduction of End points in Non-insulin-dependent diabetes mellitus with the Angiotensin II Antagonist (RENAAL) study, losartan decreased the number of patients reaching the primary end point of a composite of measures of neuropathy. The relative risk reduction was ~ 15% with losartan and this was due to a reduction in both the doubling of creatinine concentration (25%) and of ESRD (28%) but not in death. In the Irbesartan Diabetic Nephropathy Trial (IDNT), the beneficial effect of irbesartan was mainly against the doubling of the baseline creatinine concentration (37% risk reduction) but there was also a 20% reduction in the onset of ESRD. Irbesartan had no effect on mortality. Beneficial effects occurred in addition to blood pressure being controlled by agents other than the AT1 antagonists. These clinical trials suggest that there may be a class renoprotective action with AT1 antagonists, although the mechanism is not clear. Patients with Type 2 diabetes and nephropathy should receive either an AT1 antagonist or the angiotensin converting enzyme inhibitor ramipril to ensure renoprotection.

Crohn's disease with oral presenting signs masquerading as chronic osteomyelitis

Background: A case of Crohn's disease (CD) was diagnosed following recognition of oral and systemic signs and symptoms in a 19-year-old male patient. Methods: Clinical investigation utilized included blood tests (full blood count, electrolytes, urea, creatinine, liver function tests), computed tomogrphy scans, magnetic resonance imaging scans, oral biopsies, colonoscopy and biopsies of the terminal ileum and colon. Results: A diagnosis of CD was made which then allowed appropriate medical treatment to be initiated. Conclusion: The importance of a thorough medical history and full physical examination with appropriate investigations as dictated by clinical findings is demonstrated.

Evaluation of cyclooxygenase 2 inhibitor use in patients admitted to a large teaching hospital

Background: The heavy usage of coxibs in Australia far outstrips the predicted usage that was based on the treatment of patients with risk factors for upper gastro-intestinal adverse events from conventional anti--inflammatory agents. This raises questions regarding the appropriateness of prescribing. Aims: To determine: (i) the relationship between prescriptions for cyclooxygenase 2 (COX-2) inhibitors and objective evidence of inflammatory arthritis, (ii) prior experience with paracetamol and/or conventional non-steroidal anti-inflammatory drugs (NSAIDs), and (iii) contraindications to the use of NSAIDs. Methods: Drug utilization evaluation and rheumato-logical assessment was conducted on 70 consecutive patients admitted on COX-2 inhibitors to a 480-bed metropolitan hospital. The main outcome measures were: the indication for COX-2 inhibitor; objective -evidence of inflammatory arthritis; previous trial of -paracetamol or conventional NSAIDs; and patient -satisfaction. Results: Only 11 patients (16%) had symptoms or signs of an inflammatory arthropathy, and met Pharmaceut-ical Benefits Schedule criteria for prescribing a COX-2 inhibitor. Fifty-nine patients (84%) had chronic osteo-arthritis, degenerative spinal disease, injury or malignancy, without overt active inflammation. Fourteen patients (20%) had trialled regular paracetamol prior to using any NSAID treatment. Conventional NSAIDs had been previously used by 51 patients (73%). Eleven patients (16%) reported previous adverse gastrointestinal effects from conventional NSAIDs. On the basis of significant renal impairment (creatinine clearance 5/10). Conclusions: Drug utilization data indicate that COX-2 inhibitors are frequently used first line for degenerative osteoarthritis in the absence of overt inflammation, without prior adequate trial of paracetamol and with disregard for the cautions and contraindications of these agents. These findings may explain the unprecedented Pharmaceutical Benefits Schedule expenditure on COX-2 inhibitors in Australia.

Control of familial and renal cardiac diseases in English bull terriers: How to repair a damaged breed?

Control recommendations are presented for four genetic or familial diseases that cause significant morbidity and mortality in affected English Bull Terriers. Bull Terrier polycystic kidney disease is an autosomal dominant disease diagnosed by detecting a minimum of three renal cysts, with cysts present in both kidneys, and similarly affected family members to confirm the inherited nature of the cysts. Bull Terrier hereditary nephritis is an autosomal dominant disease diagnosed in otherwise normal animals with urinary protein: creatinine ratios persistently >0.3 and no significant urinary sediment, a family history of the disease, and characteristic glomerular basement membrane lesions. Mitral valve myxomatous degeneration and left ventricular outflow tract obstruction in Bull Terriers are familial diseases diagnosed by auscultating characteristic murmurs in affected animals. Excluding animals with these clinical signs from the breeding pool will reduce the prevalence rates of these diseases, however maintenance of an effective population size is also important. Providing breeders with information on genetics, including the risks associated with inbreeding and the benefits of outcrossing, is likely to improve canine breeding practices, thus increasing fitness and fecundity of these purebred dogs.

Correlação entre a depuração plasmática de creatinina utilizando urina coletada durante 24 horas e 12 horas

Introdução: A concentração da creatinina no plasma é usada para avaliar a função renal, mas a depuração da creatinina plasmática (DCP) constitui método mais sensível para essa finalidade. Objetivo: Correlacionar a DCP em coleta urinária de 12 horas noturna com a de 24 horas. Métodos: Noventa e cinco voluntários (34-64 anos) coletaram urina durante 24 horas em dois frascos: diurno (das 7h às 19h) e noturno (das 19h às 7h do dia seguinte). A coleta de sangue se deu em jejum para medidas bioquímicas. A correlação entre as variáveis foi feita pelo teste Pearson (r) e a concordância de medidas, pelo teste de Bland-Altman. Resultados: Urinas de quatro indivíduos foram recusadas por erro de coleta. Na amostra final (n = 91; 42 homens), havia 23 hipertensos e cinco diabéticos. A DCP (mL/min/1,73 m2) foi menor no período noturno em mulheres (77,8 ± 22,7 versus 88,4 ± 23,6; p < 0,05) e similar em homens (91,2 ± 22,9 versus 97,3 ± 30,9; p > 0,05). As correlações entre a DCP na urina de 12 horas noturna ou diurna e a de 24 horas foram fortes (r = 0,85 e 0,83, respectivamente). Em 85 e 83 dos 91 indivíduos, a medida da DCP noturna e diurna, respectivamente, foi concordante com a de 24 horas. Conclusão: A urina de 12 horas, sobretudo quando coletada à noite, fornece valores de DCP similares àqueles obtidos em coleta de 24 horas. Como essa coleta é mais fácil de ser feita em pacientes ambulatoriais à noite, esse período deveria ser preferido para a medida da filtração glomerular.

Hippuric acid in urine: reference values

OBJECTIVE: To establish reference values for hippuric acid (HA) excreted in the urine, and to evaluate the impact of age, gender, alcohol, and tobacco, on these levels in a population nonexposed to toluene. METHODS: Reference values for hippuric acid in urine were determined in 115 toluene nonexposed healthy volunteers, from Alfenas city, Southeastern Brazil. A questionnaire was applied to each volunteer and data on occupational and personal habits were collected. Biochemical and hematological analyses were used to confirm the volunteers' good health condition. Reference values were expressed in g HA/g urine creatinine, as mean ± standard deviation (x ± SD), median, 95% confidence interval (95%CI), 95th percentile, and upper reference value (URV, mean +2 SD). RESULTS: Reference values of hippuric acid in urine were: mean ± standard deviation =0.18±0.10; median =0.15; 95% confidence interval =0.16±0.20; 95th percentile = 0.36 and upper reference value (URV, mean +2 SD) =0.38. Statistically significant differences in urinary HA (Wilcoxon - Mann/Whitney, p<0.05) were observed for different genders and age groups. Alcohol ingestion and smoking habit did not significantly affect the results. CONCLUSIONS: The reference values of hippuric acid in urine can be used in biomonitoring programs of workers occupationally exposed to toluene, especially in the southern region of the state of Minas Gerais. Age and gender may affect the HA reference values.

Molecularly-imprinted materials for potentiometric transduction: application to the antibiotic enrofloxacin

Enrofloxacin (ENR) is an antimicrobial used both in humans and in food producing species. Its control is required in farmed species and their surroundings in order to reduce the prevalence of antibiotic resistant bacteria. Thus, a new biomimetic sensor enrofloxacin is presented. An artificial host was imprinted in specific polymers. These were dispersed in 2-nitrophenyloctyl ether and entrapped in a poly(vinyl chloride) matrix. The potentiometric sensors exhibited a near-Nernstian response. Slopes expressing mVΔlog([ENR]/M) varied within 48–63. The detection limits ranged from 0.28 to 1.01 µg mL 1. Sensors were independent from the pH of test solutions within 4–7. Good selectivity was observed toward potassium, calcium, barium, magnesium, glycine, ascorbic acid, creatinine, norfloxacin, ciprofloxacin, and tetracycline. In flowing media, the biomimetic sensors presented good reproducibility (RSD of ±0.7%), fast response, good sensitivity (47 mV/Dlog([ENR]/ M), wide linear range (1.0×10-5–1.0×10-3 M), low detection limit (0.9 µg mL-1), and a stable baseline for a 5×10-2 M acetate buffer (pH 4.7) carrier. The sensors were used to analyze fish samples. The method offered the advantages of simplicity, accuracy, and automation feasibility. The sensing membrane may contribute to the development of small devices allowing in vivo measurements of enrofloxacin or parent-drugs.

Ciprofloxacin-imprinted polymeric receptors as ionophores for potentiometric transduction

A 3D-mirror synthetic receptor for ciprofloxacin host–guest interactions and potentiometric transduction is presented. The host cavity was shaped on a polymeric surface assembled with methacrylic acid or 2-vinyl pyridine monomers by radical polymerization. Molecularly imprinted particles were dispersed in 2-nitrophenyl octyl ether and entrapped in a poly(vinyl chloride) matrix. The sensors exhibited a near-Nernstian response in steady state evaluations. Slopes and detection limits ranged from 26.8 to 50.0mVdecade−1 and 1.0×10−5 to 2.7×10−5 mol L−1, respectively. Good selectivity was observed for trimethoprim, enrofloxacin, tetracycline, cysteine, galactose, hydroxylamine, creatinine, ammonium chloride, sucrose, glucose, sulphamerazine and sulfadiazine. The sensors were successfully applied to the determination of ciprofloxacin concentrations in fish and in pharmaceuticals. The method presented offered the advantages of simplicity, accuracy, applicability to colored and turbid samples and automation feasibility, as well as confirming the use of molecularly imprinted polymers as ionophores for organic ion recognition in potentiometric transduction.

Biomimetic sensors of molecularly-imprinted polymers for chlorpromazine determination

A new man-tailored biomimetic sensor for Chlorpromazine host-guest interactions and potentiometric transduction is presented. The artificial host was imprinted within methacrylic acid, 2-vinyl pyridine and 2-acrylamido-2-methyl-1-propanesulfonic acid based polymers. Molecularly imprinted particles were dispersed in 2-nitrophenyloctyl ether and entrapped in a poly(vinyl chloride) matrix. Slopes and detection limits ranged 51–67 mV/decade and 0.46–3.9 μg/mL, respectively, in steady state conditions. Sensors were independent fromthe pHof test solutionswithin 2.0–5.5.Good selectivitywas observed towards oxytetracycline, doxytetracycline, ciprofloxacin, enrofloxacin, nalidixic acid, sulfadiazine, trimethoprim, glycine, hydroxylamine, cysteine and creatinine. Analytical features in flowing media were evaluated on a double-channel manifold, with a carrier solution of 5.0×10−2 mol/L phosphate buffer. Near-Nernstian response was observed over the concentration range 1.0×10−4 to 1.0×10−2 mol/L. Average slopes were about 48 mV/decade. The sensors were successfully applied to field monitoring of CPZ in fish samples, offering the advantages of simplicity, accuracy, automation feasibility and applicability to complex samples.

Man-tailored biomimetic sensor of molecularly imprinted materials for the potentiometric measurement of oxytetracycline

A novel biomimetic sensor for the potentiometric transduction of oxytetracycline is presented. The artificial host was imprinted in methacrylic acid and/or acrylamide based polymers. Different amounts of molecularly imprinted and non-imprinted polymers were dispersed in different plasticizing solvents and entrapped in a poly(vinyl chloride) matrix. Only molecularly imprinted based sensors allowed a potentiometric transduction, suggesting the existence of host–guest interactions. These sensors exhibited a near-Nernstian response in steady state evaluations; slopes and detection limits ranged 42–63 mV/decade and 2.5–31.3 µg/mL, respectively. Sensors were independent from the pH of test solutions within 2–5. Good selectivity was observed towards glycine, ciprofloxacin, creatinine, acid nalidixic, sulfadiazine, cysteine, hydroxylamine and lactose. In flowing media, the biomimetic sensors presented good reproducibility (RSD of ±0.7%), fast response, good sensitivity (65 mV/decade), wide linear range (5.0×10−5 to 1.0×10−2 mol/L), low detection limit (19.8 µg/mL), and a stable baseline for a 5×10−3M citrate buffer (pH 2.5) carrier. The sensors were successfully applied to the analysis of drugs and urine. This work confirms the possibility of using molecularly imprinted polymers as ionophores for organic ion recognition in potentiometric transduction.

Subacute effects of the thiodicarb pesticide on target organs of male wistar rats: biochemical, histological, and flow cytometry studies

Thiodicarb, a carbamate pesticide widely used on crops, may pose several environmental and health concerns. This study aimed to explore its toxicological profile on male rats using hematological, biochemical, histopathological, and flow cytometry markers. Exposed animals were dosed daily at 10, 20, or 40 mg/kg/body weight (group A, B, and C, respectively) during 30 d. No significant changes were observed in hematological parameters among all groups. After 10 d, a decrease of total cholesterol levels was noted in rats exposed to 40 mg/kg. Aspartate aminotransferase (AST) activity increased (group A at 20 d; groups A and B at 30 d) and alkaline phosphatase (ALP) (group B at 30 d) activity significantly reduced. At 30 d a decrease of some of the other evaluated parameters was observed with total cholesterol and urea levels in group A as well as total protein and creatinine levels in groups A and B. Histological results demonstrated multi-organ dose-related damage in thiodicarb-exposed animals, evidenced as hemorrhagic and diffuse vacuolation in hepatic tissue; renal histology showed disorganized glomeruli and tubular cell degeneration; spleen was ruptured with white pulp and clusters of iron deposits within red pulp; significant cellular loss was noted at the cortex of thymus; and degenerative changes were observed within testis. The histopathologic alterations were most prominent in the high-dose group. Concerning flow cytometry studies, an increase of lymphocyte number, especially T lymphocytes, was seen in blood samples from animals exposed to the highest dose. Taken together, these results indicate marked systemic organ toxicity in rats after subacute exposure to thiodicarb.

Fulminant hepatitis: a clinical review of 11 years

24 cases of fulminant hepatitis (FH) hospitalized in the Clínica de Doenças Infecciosas e Parasitárias do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo during the period from January 1976 to December 1986 were reviewed from their clinical, epidemiological and laboratorial aspects. 88% of the patients died; 20 patients (83%) presented hemorrhages and, of these, 19 died. Bacterial infections occurred in 14 patients (58%) all of whom died. Ascitis was noted in 3 cases; cerebral edema was present in 16 cases. Maximal ALT levels for each patient during hospitalization ranged widely from 81 to 4,460 UI/l. Thirteen patients presented high creatinine levels (54%). Prothrombin time activity ranged from 2.1% to 67%. Fever was present in 20 cases (83%). Encephalopathy occurred within the first 2 weeks of illness in 72% of the cases. In 7 cases other illnesses were present. The etiology could not be determined in 13 cases. In 3 cases it was due to yellow fever and 6 cases were caused by viruses other than yellow fever. In one case the cause was drug usage and in another case, possibly alcohol. The authors believe that the clinical definition of FH requires further discussion before it is established. In this study FH is a young person's disease. The mortality found was similar to that by other authors. Factors that contributed to death were: hemorrhages and bacterial infection. Factors that worsened the prognosis of hepatitis were: associated illnesses and surgical procedure. The levels of ALT during hospitalization did not correlate well with the severity of the hepatitis. The authors believe that yellow fever should be considered a cause of FH where the clinical picture meets the criteria for such, although its mechanisms of encephalopathy remain obscure. The clinical details of the 3 cases of yellow fever are presented.

Characterization of the Toxicological Effects of Aminocarb on Rats: Hematological, Biochemical, and Histological Analyses

Aminocarb is a widely applied carbamate insecticide with action of controlling pests such as Lepidoptera and Coleoptera. In this study, subchronic effects on Wistar rats were investigated using hematological, biochemical, and histological techniques. Rats were exposed orally at sublethal levels of 10, 20, or 40 mg/kg body weight (groups A, B, and C, respectively) for 14 d. Hematological results revealed no statistical differences after 1 d of exposure but significant reduction in white blood cells detected after 7 d of exposure in group C, as well as, in all treated groups after 14 d of exposure. Biochemical data showed a decrease of acetylcholinesterase activity in all groups after 1 d of exposure with a return to normal after 7 and 14 d. Significant increase in alkaline phosphatase activity of rats exposed to aminocarb was noted after 7 d of treatment. The levels of triglycerides were also significantly decreased. The present investigation also showed a significant increase in content of serum urea and creatinine in animals from group A (14 d), and from groups B and C (7 and 14 d). Histological results demonstrated hemorrhagic focus on hepatic and renal parenchyma in all exposed groups. Taken together, the attained results were dose dependent and indicated adverse effects of aminocarb on hepatic and renal functions, as well as on immune responsiveness at sublethal tested doses.

Is rhabdomyolysis an additional factor in the pathogenesis of acute renal failure in leptospirosis?

Leptospirosis is an important cause of acute renal failure in our environment. Although several mechanisms are implicated, the role of rhabdomyolysis in the pathogenesis of acute renal failure in leptospirosis has not been analysed. Sixteen patients with the diagnosis of leptospiroses consecutively admitted to the hospital were prospectively studied. The disease was characterized by sudden onset in all patients and, at admission, jaundice, conjunctival suffusion and myalgias. Mild to moderate proteinuria with unremarkable urinary sediment was recorded in 37.5% of the patients and abnormal levels of urea creatinine were found in 87.5% and 74.0%, respectively. Increased levels of aminotranspherase were documented in all 12 and CPK in all 10 patients studied. Serum myoglobin levels greater than 120µg/l recorded in 56.2%. A correlation between myoglobin and renal failure or severity of disease, however, could not be established.

NEPHROTOXICITY ATTRIBUTED TO MEGLUMINE ANTIMONIATE (GLUCANTIME) IN THE TREATMENT OF GENERALIZED CUTANEOUS LEISHMANIASIS

Background: Pentavalent antimonials have became of basic importance for the treatment of leishmaniasis. Their most severe side effects have been reported to be increased hepatic enzyme levels and electrocardiographic abnormalities. Nephrotoxicity has been rarely related. Observations: We report a case of generalized cutaneous leishmaniasis involving a 50-year old male patient who was submitted to treatment with meglumine antimoniate (Glucantime). He developed acute renal failure (ARF) due to acute tubular necrosis (ATN), followed by death after receiving a total of 53 ampoules of Glucantime. Conclusions: The treatment with Glucantime was responsible by ARF diagnosed in this patient. The previous urine osmolarity and serum creatinine levels were normal and the autopsy showed ATN. It should be pointed out if ARF may also be explained by massive deposits of immunocomplexes by leishmania antibodies and antigens due to the antigenic break by the antimonial compound, since our patient presented countless lesions covering the entire tegument, similar to the Hexheimer phenomenon, but at the autopsy no glomerular alterations were seen.