IL33 and IL1RL1 variants are associated with asthma and atopy in a Brazilian population.

Atopic asthma is a chronic inflammatory disease in airways resulting from genetic and environmental factors, characterized by production of the Th2 cytokines interleukin-4 (IL-4), interleukin-5 (IL-5) and interleukin-13 (IL-13). Interleukin-33 (IL-33) appears to be a potent inducer of Th2 immune response. This occurs when IL-33 binds and activates its receptor, the membrane ST2 (ST2L) in mast cells, dendritic cells, basophils, eosinophils, innate lymphoids and Th2 cells, leading to the release of these cytokines and intensifying allergic inflammation. Polymorphisms in the IL33 and IL1RL1 can act as protective or risk factors for asthma and/or allergy in humans. No study was conducted to replicate such findings in a European and African descendent mixed population. DNA was extracted from peripheral blood from 1223 subjects, and the samples were genotyped using Illumina 2.5 Human Omni Beadchip. We tested for possible associations between SNPs in the IL33 and ST2 with asthma and allergy markers such as specific IgE (sIgE), IL-5 and IL-13 production and skin prick test (SPT). Logistics regressions were performed using PLINK software 1.07. The analyses were adjusted for sex, age, helminth infection and ancestry markers. The G allele of IL33 SNP rs12551256 was negatively associated with asthma (OR 0.71, 95% CI: 0.53-0.94, P = 0.017). In contrast, the A allele of IL1RL1 rs1041973 was positively associated with IL-5 production (OR 1.36, 95% CI: 1.09-1.84, P = 0.044), sIgE levels (OR 1.40, 95% CI: 1.07-1.84, P = 0.013) and positive SPT (OR 1.48, 95% CI: 1.08-2.03, P = 0.014), for Blomia tropicalis mite. The same allele, in atopic subjects, was associated with decreased production of soluble ST2 (sST2) (P < 0.05). Moreover, expression quantitative trait loci (eQTL) analysis suggests that rs1041973 and rs873022 regulate the expression of IL1RL1 gene. This latest SNP, rs873022, the T allele, was also associated with a lower production of sST2 in plasma of Brazilians. The genetic risk score for rs1041973 and rs16924161 demonstrated a higher risk for SPT positivity against B. tropicalis, the greater the number of risk alleles for both SNPs. Our findings demonstrate a robust association of genetic variants in IL1RL1 and IL33 SNPs with allergy markers and asthma.

Oocyte viability and cortical activation under different salt solutions in Prochilodus lineatus (Teleostei: Prochilodontidae).

This study aimed to evaluate the effect of five salt solutions in the maintenance of morphological features of cortical alveolus, hydration and fertilization capacity of Prochilodus lineatus oocytes. For this purpose, five saline solutions were tested: Ringer's solution, Ringer's lactate solution, Hank's balanced salt solution (HBSS), Hank's balanced salt solution without calcium (HBSS without calcium) and solution for salmonid eggs. Oocytes were maintained for 2 hr in saline solution with controlled temperature subsequently evaluated for hydration, cortical activation and fertilization ability. In the evaluation of the fertilization ability, two controls were used: C1-fertilized oocytes after extrusion-and C2-oocytes kept in ovarian fluid and fertilized after 2 hr. There was a significant reduction in the viability of oocytes C2 (28.8% ± 12.9%) compared to C1 (65.3% ± 26.7%), and no significant differences were found between treatments HBSS and HBSS without calcium and C2. Only HBSS and HBSS without calcium maintained the non-activated state of the gametes, with a fertilization rate of 16.4% ± 6.7% and 5.6% ± 2.3%, respectively; however, they did not extend the viability of oocytes, such that they continued to undergo degradation during the storage period, similar to oocytes retained only in ovarian fluid.

The use of pain scales in small animal veterinary practices in the USA.

OBJECTIVES: Pain assessment in veterinary medicine is challenging. Uncertainty in the ability to recognise pain in animals contributes to suboptimal analgesia. Pain scales have been developed to aid in pain recognition. It is unknown if such scales are routinely utilised in veterinary practices. MATERIALS AND METHODS: A survey using RedCap software was emailed to veterinarians and veterinary technicians working in practices across the USA. This study aimed to investigate whether pain scoring was routinely performed and reasons to use or not use pain scales. One hundred and forty-four participants were required to estimate prevalence (95% confidence level, 5% precision) with hypothesised prevalence of approximately 10%. RESULTS: One hundred and forty-seven participants completed the survey. Seventy (47.6%) responded that pain scoring was performed in their practices, 24 (16.3%), reported "sometimes" and 53 (36.1%) reported pain scores were not performed. Reasons for not pain scoring included no training (51.9%) and busy caseload (48.1%). Disadvantages of pain scales were unreliability (16/82; 20%), duration required for completion (14/82; 17%) and vocalisation (14/82; 17%). CLINICAL SIGNIFICANCE: Almost 50% of the small animal practices surveyed reported the use of pain scales as part of their routine workflow. However, many practices still do not consistently utilise pain scales to assess pain in dogs and cats. Perceived unreliability and lack of compliance were reasons for this result. Improvement of training and proper pain scale introduction and implementation in small animal practices in the USA appears to be required.

Braylin induces a potent vasorelaxation, involving distinct mechanisms in superior mesenteric and iliac arteries of rats.

Arterial hypertension is a risk factor for various cardiovascular and renal diseases, representing a major public health challenge. Although a wide range of treatment options are available for blood pressure control, many hypertensive individuals remain with uncontrolled hypertension. Thus, the search for new substances with antihypertensive potential becomes necessary. Coumarins, a group of polyphenolic compounds derived from plants, have attracted intense interest due to their diverse pharmacological properties, like potent antihypertensive activities. Braylin (6-methoxyseselin) is a coumarin identified in the Zanthoxylum tingoassuiba species, described as a phosphodiesterase-4 (PDE4) inhibitor. Although different coumarin compounds have been described as potent antihypertensive agents, the activity of braylin on the cardiovascular system has yet to be investigated. To investigate the vasorelaxation properties of braylin and its possible mechanisms of action, we performed in vitro studies using superior mesenteric arteries and the iliac arteries isolated from rats. In this study, we demonstrated, for the first time, that braylin induces potent vasorelaxation, involving distinct mechanisms from two different arteries, isolated from rats. A possible inhibition of phosphodiesterase, altering the cyclic adenosine monophosphate (cAMP)/cAMP-dependent protein kinase (PKA) pathway, may be correlated with the biological action of braylin in the mesenteric vessel, while in the iliac artery, the biological action of braylin may be correlated with increase of cyclic guanosine monophosphate (cGMP), followed by BKCa, Kir, and Kv channel activation. Together, these results provide evidence that braylin can represent a potential therapeutic use in preventing and treating cardiovascular diseases.

Renal disorders involved in the pathophysiology of urinary excretion of a-1 microglobulin in patients with glomerulopathies.

AIMS: The protein alpha1-microglobulin (alpha1-microg) is filtered by the glomeruli and fully reabsorbed by the proximal tubules, and tubulointerstitial injury compromises its reabsorption. The aim of this study was to determine which functional, morphological and inflammatory renal disorders associated with tubulointerstitial damage interfere with urinary excretion of alpha1-microg in patients with glomerulopathies. PATIENTS AND METHODS: 38 patients (33.6 +/- 11.3 years) with primary or secondary glomerulopathies diagnosed by renal biopsies were studied. The urinary fractional excretion of alpha1-microg (FEalpha1-microg), the urinary monocyte chemoattractant protein-1/urinary creatinine (UMCP-1) index and 24-h proteinuria were determined. In the cortex of renal biopsies, the number of macrophages/104 microm2 of glomerular tuft (GT) and tubulointerstitial (TI) areas, the relative interstitial area (RCIA), and the relative interstitial fibrosis area (CIF) were measured. Results are reported as median and range and the Spearman non-parametric test was used to determine the correlations. RESULTS: FEalpha1-microg was 0.165% (0.008% - 14,790.0%) in patients with glomerulopathies and 0.065% (0.010% - 0.150%) in the control group (p < 0.05; Mann-Whitney U-Test). FEalpha1-microg was correlated with creatinine clearance (r = -0.4396; p = 0.0358), UMCP-1 index (r = 0.5978; p < 0.0001), number of macrophages/TI area (r = 0.5634; p = 0.0034) and RCIA (r = 0.7436; p < 0.0001). However, FEa1-microg was not correlated with proteinuria (r = 0.1465; p = 0.5153) or with CIF (r = 0.0039; p = 0.98). CONCLUSIONS: renal MCP-1 and the expansion and number of macrophages of the tubulointerstitial area participate in the increase of urinary excretion of alpha1-microg in patients with glomerulopathies. Although proteinuria and interstitial fibrosis have not been associated with this effect, the present study does not exclude some of these disorders in the pathophysiology of urinary excretion of alpha1-microg.

Mast cells, TGF-beta1 and alpha-SMA expression in IgA nephropathy.

IgA nephropathy (IgAN) is a kidney disease with a varying renal prognosis. Recently, many studies have demonstrated that renal alpha-smooth muscle actin (alpha-SMA) and transforming growth factor (TGF-beta1) expression, as well interstitial mast cell infiltrates could represent a prognostic marker in several renal diseases. The aim of our study was to analyze the prognostic value of mast cell, TGF-beta1 and alpha-SMA expression in IgAN. A survey of the medical records and renal biopsy reports of 62 patients with a diagnosis of IgAN followed-up from 1987 to 2003 was performed. The mean follow-up time was 74.7 +/- 50.0 months. The immunohistochemical studies were performed using a monoclonal antibody anti-human mast cell tryptase, a polyclonal antibody anti-human TGF-beta1, and a monoclonal antibody anti-human alpha-SMA. An unfavorable clinical course of IgAN was related to interstitial mast cell infiltrates and alpha-SMA expression in the tubulointerstitial area. Expression of glomerular TGF-beta1 and alpha-SMA, and interstitial TGF-beta1 is not correlated with clinical course in IgAN. In conclusion, the increased number of mast cells and higher alpha-SMA expression in the tubulointerstitial area may be predictive factors for the poor prognosis of patients with IgAN.

Increased expression of p38 mitogen-activated protein kinase is related to the acute renal lesions induced by gentamicin.

Mitogen-activated protein kinases (MAPK) may be involved in the pathogenesis of acute renal failure. This study investigated the expression of p-p38 MAPK and nuclear factor kappa B (NF-kappaB) in the renal cortex of rats treated with gentamicin. Twenty rats were injected with gentamicin, 40 mg/kg, i.m., twice a day for 9 days, 20 with gentamicin + pyrrolidine dithiocarbamate (PDTC, an NF-kappaB inhibitor), 14 with 0.15 M NaCl, i.m., twice a day for 9 days, and 14 with 0.15 M NaCl , i.m., twice a day for 9 days and PDTC, 50 mg kg(-1) day(-1), i.p., twice a day for 15 days. The animals were killed 5 and 30 days after the last of the injections and the kidneys were removed for histological, immunohistochemical and Western blot analysis and for nitrate determination. The results of the immunohistochemical study were evaluated by counting the p-p38 MAPK-positive cells per area of renal cortex measuring 0.05 mm2. Creatinine was measured by the Jaffé method in blood samples collected 5 and 30 days after the end of the treatments. Gentamicin-treated rats presented a transitory increase in plasma creatinine levels. In addition, animals killed 5 days after the end of gentamicin treatment presented acute tubular necrosis and increased nitrate levels in the renal cortex. Increased expression of p-p38 MAPK and NF-kappaB was also observed in the kidneys from these animals. The animals killed 30 days after gentamicin treatment showed residual areas of interstitial fibrosis in the renal cortex, although the expression of p-p38 MAPK in their kidneys did not differ from control. Treatment with PDTC reduced the functional and structural changes induced by gentamicin as well as the expression of p-p38 MAPK and NF-kappaB. The increased expression of p-p38 MAPK and NF-kappaB observed in these rats suggests that these signaling molecules may be involved in the pathogenesis of tubulointerstitial nephritis induced by gentamicin.

Body temperature measurements in pigs during general anaesthesia.

The aim was to compare rectal, pharyngeal and oesophageal temperature measurements in anaesthetized pigs. Data were compared using the Bland-Altman method, and correlation coefficients and error measures were calculated. Sixty-six sets of data were collected from 16 pigs weighing 16.2 ± 4.2 kg. The bias (and 95% limit of agreement) for rectal and pharyngeal compared with oesophageal temperature were 0.69 (-1.18 to 2.57) ℃ and 0.22 (-0.84 to 1.28) ℃, respectively. The correlation coefficients for rectal and pharyngeal compared with oesophageal temperature were 0.47 and 0.87, respectively. The absolute error for rectal and pharyngeal compared with oesophageal temperature was 0.7 ± 0.9℃ and 0.2 ± 0.5℃, respectively. Pharyngeal temperature measurement may be more suitable than rectal temperature measurement for estimation of oesophageal temperature during general anaesthesia of pigs.

Alpha-SM actin expression as prognostic indicator in IgA nephropathy (Berger's disease).

Recent studies have demonstrated that alpha-Smooth Muscle actin expression in glomerular and tubulointerstitial compartments of renal tissue could represent a prognostic marker in several renal diseases. Our objective was to identify the prognostic value of alpha-SM actin actin expression on the evolution of renal damage in Primary IgA nephropathy (Berger's disease). 43 patients followed up from 1988 to 1999 at the University Hospital, Faculty of Medicine of Ribeirão Preto, University of Sao Paulo, Brazil, was studied. Clinical-laboratory data were obtained from the medical records of the patients using a protocol containing name, race, gender, origin, profession, age at clinical presentation of the disease and personal and family history. The parameters assessed in the approach to IgA nephropathy were serum creatinine, creatinine clearance, serum albumin, total serum protein, 24 hours proteinuria, glycaemia, serum sodium, potassium, calcium and phosphorus ions, analysis of urinary sediment, serum complement profile, blood count, and renal biopsy. Morphological evaluation was performed by renal biopsy using common light and immunofluorescence microscopy. Immunohistochemical studies were performed using a murine monoclonal antibody to alpha-SM actin. Our data showed that alpha-SM actin expression in the glomerular and tubulointerstitial compartments are not correlated with unfavorable clinical course of primary IgA nephropathy.

Preoperative factors associated with hypotension in young anaesthetised dogs undergoing elective desexing.

OBJECTIVES: Document the proportion of dogs with perioperative hypotension and explore the association of sex, age and body mass and indices of hydration with mean arterial blood pressure (MAP) in two cohorts of young, healthy anaesthetised dogs. METHODS: Dogs were anaesthetised with a standardised protocol. The proportion of dogs with invasively measured MAP <60 mmHg for ≥10 min was recorded. The area under the MAP*time curve (MAP-AUC) was calculated for a standard perioperative period. The association of explanatory variables, including sex, age, body mass and indices of hydration (urine specific gravity (USG), packed cell volume and total solids) measured prior to surgery, with the MAP-AUC was explored using regression analysis in the first cohort (n = 71) and externally validated in the second cohort (n = 24). RESULTS: In cohort 1, 35 of 71 dogs (0.49, 95% confidence interval (CI) 0.37-0.61) dogs and 17/24 dogs in cohort 2 (0.71, 95% CI 0.53-0.89) developed hypotension. Regression analysis showed that age and USG were significantly associated with MAP-AUC for cohort 1 (P = 0.0138). There was a positive association of MAP-AUC with age and a negative association with USG. The association of MAP-AUC with USG was supported in cohort 2, with a significant negative association (P = 0.014, r = -0.54) CONCLUSION: The high frequency of hypotension in both cohorts supports blood pressure monitoring during anaesthesia of young, healthy dogs. USG, an index of hydration, appears negatively associated with MAP during anaesthesia, suggesting that subclinical dehydration may contribute to lower MAP during surgical anaesthesia.

Nitric oxide inhibits irreversibly P815 cell proliferation: involvement of potassium channels.

Nitric oxide (NO) has been shown to inhibit both normal and cancer cell proliferation. Potassium channels are involved in cell proliferation and, as NO activates these channels, we investigated the effect of NO on the proliferation of murine mastocytoma cell lines and the putative involvement of potassium channels. NO (in the form of NO donors) caused dose-dependent inhibition of cell proliferation in the P815 cell line inducing growth arrest in the mitosis phase. Incubation with NO donor for 4 or 24 h had a similar inhibitory effect on cell proliferation, indicating that this effect is irreversible. The inhibitory effect of NO was completely prevented by the blockade of voltage- and calcium-dependent potassium channels, but not by blockade of ATP-dependent channels. NO inhibition of cell proliferation was unaffected by guanylate cyclase and by cytoskeleton disruptors. Therefore, NO inhibits cell proliferation irreversibly via a potassium channel-dependent but guanylate cyclase-independent pathway in murine mastocytoma cells.

Sodium bicarbonate treatment reduces renal injury, renal production of transforming growth factor-beta, and urinary transforming growth factor-beta excretion in rats with doxorubicin-induced nephropathy.

The aim of this study is to investigate the effect of sodium bicarbonate on doxorubicin-injected rats. Thirty female Wistar rats were injected with doxorubicin (3.5 mg/kg of body weight, intravenously) and 30 rats with 0.15 mol/L of sodium chloride solution (group C). Fifteen days later, we replaced the drinking water with a 0.15-mol/L sodium bicarbonate solution for 10 of the animals injected with doxorubicin (group AD-B). Three months after the beginning of treatment, urine samples were collected to quantify albumin, creatinine, and transforming growth factor-beta (TGF-beta). The rats were killed, and the kidneys were removed for histological, morphometric, immunohistochemical, and RNA studies. All doxorubicin-injected animals showed structural renal changes. However, these alterations were less intense in rats treated with doxorubicin plus sodium bicarbonate (P < 0.05). The percentage of glomerulosclerosis was 0.11% +/- 0.08% in group C, 14.7% +/- 12.8% in group AD (rats treated with doxorubicin only), and 4.38% +/- 1.9% in group AD-B, and the percentage of tubulointerstitial damage was 0. 01% +/- 0.03% in group C, 54.6% +/- 20.3% in group AD, and 16.6% +/- 10.3% in group AD-B. The immunostaining for TGF-beta in the renal cortex and glomeruli was more intense in the animals injected with doxorubicin only. A greater renal cortical TGF-beta messenger RNA content was observed in the animals injected with only doxorubicin that did not receive sodium bicarbonate (P < 0.05). These animals also presented a greater rate of urinary TGF-beta excretion reported as picograms of TGF-beta per milligram of urinary creatinine (P < 0.05), which was 202 +/- 11 pg/mg in group C, 1, 103 +/- 580 pg/mg in group AD, and 299 +/- 128 pg/mg in group AD-B. However, albuminuria was more intense in the sodium bicarbonate-treated animals (P < 0.05). The animals from group AD also showed higher immunostaining scores for vimentin and albumin in tubule cells (P < 0.05). In conclusion, treatment with sodium bicarbonate reduces structural renal damage, albumin reabsorption, and renal TGF-beta production in rats with doxorubicin-induced nephropathy.

Rhabdomyonecrosis experimentally induced in Wistar rats by Africanized bee venom.

Damage is reported to skeletal muscle experimentally induced in Wistar rats by Africanized bee venom (ABV). Rhabdomyonecrosis was demonstrated indirectly by increased serum levels of the enzymes aspartate-aminotransferase and total creatine kinase, and directly by necrosis and inflammation observed by standard light microscopy of skeletal muscle. To our knowledge, this is the first report of a systemic damaging effect of ABV on skeletal muscle of experimentally envenomated rats. These data appear to reproduce experimentally some of the findings reported in cases of human envenomation due to multiple Africanized bee stings.

Dermal dendritic cell number correlates with serum autoantibody titers in Brazilian pemphigus foliaceus patients.

Pemphigus foliaceus (PF) is an autoimmune bullous disease endemic in Brazil. Since serum IL-12 is increased in patients with PF and Langerhans cells (LC) produce IL-12, we titrated serum autoantibodies by indirect immunofluorescence, and quantified epidermal dendritic cells, known as LC, and dermal dendritic cells (DC). Biopsies of blistering lesions were obtained from 22 patients, 13 of whom were submitted to biopsy of both injured and of apparently healthy skin. The control groups consisted of skin from 8 cadavers and from 12 women submitted to breast plastic surgery. LC and DC were identified with anti-CD1a antibody and quantified by morphometric analysis. LC number in the lesion and in apparently healthy skin from PF patients was similar to that of both control groups. DC number in the injured skin (median=0.94 DC/mm basement membrane) was higher than that of the cadaver group (median=0.13 DC/mm basement membrane). In the 13 patients with biopsies of both injured and apparently healthy skin, LC and DC were present in larger numbers in the lesion. There was a direct correlation between DC number in the lesion of the PF group and serum autoantibody titers. This correlation was not observed for LC number. The increased number of DC in the lesion, as well as its direct correlation with serum autoantibody titers suggest the participation of DC in the pathogenesis of PF. The relationship between increased DC number and IL-12 in PF needs to be clarified.

Alpha-smooth muscle actin and proliferating cell nuclear antigen expression in focal segmental glomerulosclerosis: functional and structural parameters of renal disease progression.

The aim of the present study was to investigate the expression of alpha-smooth muscle actin (alpha-SM-actin) and proliferating cell nuclear antigen (PCNA) in renal cortex from patients with focal segmental glomerulosclerosis (FSGS) and their correlations with parameters of renal disease progression. We analyzed renal biopsies from 41 patients with idiopathic FSGS and from 14 control individuals. The alpha-SM-actin immunoreaction was evaluated using a score that reflected the changes in the extent and intensity of staining in the glomerular or cortical area. The PCNA reaction was quantified by counting the labeled cells of the glomeruli or renal cortex. The results, reported as median +/- percentile (25th; 75th), showed that the alpha-SM-actin scores in the glomeruli and tubulointerstitium from the renal cortex were 2.0 (2.0; 4.0) and 3.0 (3.0; 4.0), respectively, in patients with FSGS, and 0.5 (0.0; 1.0) and 0.0 (0.0; 0.5) in the controls. The number of PCNA-positive cells per glomerulus and graded field of tubulointerstitium from the renal cortex was 0.2 (0.0; 0.4) and 1.1 (0.3; 2.2), respectively, for patients with FSGS, and 0.0 (0.0; 0.5) and 0.0 (0.0; 0.0) for controls. The present data showed an increase of alpha-SM-actin and PCNA expression in glomeruli and renal cortex from FSGS patients. The extent of immunoreaction for alpha-SM-actin in the tubulointerstitial area was correlated with the intensity of proteinuria. However, there was no correlation between the kidney expression of these proteins and the reciprocal of plasma creatinine level or renal fibrosis. These findings suggest that the immunohistochemical alterations may be reversible.

Transforming growth factor beta (TGF beta) activity in urine of patients with glomerulonephritis.

Several lines of experimental evidence have shown that transforming growth factor beta (TGF beta) may play major role in glomerular diseases, mediating the inflammatory response through glomerulosclerosis. In the present study we evaluated TGF beta activity in occasional urine samples from 7 normal individuals and from 15 patients (10 with focal glomerular sclerosis and 5 with membranous glomerulonephritis) using a CCL-64 mink lung cell growth inhibition assay. Urinary TGF beta activity (reported in relation to urine creatinine concentration, Ucr, mean +/- SD) was higher in patients with focal glomerular sclerosis (mean = 17.32 +/- 15.75/10 micrograms Ucr) and patients with membranous glomerulonephritis (mean = 17.78 +/- 11.53/10 micrograms Ucr) than in normal individuals (mean = 0.8 +/- 0.44/10 micrograms Ucr). We also observed that TGF beta activity in urine from patients with focal glomerular sclerosis correlated with their plasma creatinine levels (r = 0.85), suggesting that TGF beta activity may be correlated with other indices of disease progression. Our data suggest that measurement of urinary TGF beta activity could be a useful noninvasive procedure for the evaluation of renal TGF beta production, which may be useful to assess prognosis and to evaluate therapeutic efficacy in patients with renal disease.

Cardiac noradrenaline in experimental rat envenomation with Africanized bee venom.

The concentration of cardiac tissue noradrenaline (NOR) was determined in Wistar rats injected with 1.5 microliters/100 g body weight Africanized bee venom (ABV) (LD50 = 0.8 microliter/100 g body weight by the intravenous route). The animals were injected with ABV by the intramuscular (IM), intraperitoneal (IP), subcutaneous (SC) and intravenous (IV) routes. Animals injected by the IM, IP and SC routes were sacrificed 4, 7 and 24 hours after injection. The animals injected by the IV route were sacrificed when they became apnoeic (within minutes). NOR levels in animals injected by the IM, IP and SC routes were inconstant and inconclusive. In contrast, animals injected with ABV by the IV route showed a significant decrease in NOR concentration when compared to their respective controls, suggesting tissue NOR release. It is suggested that the mechanism of death of the animals injected IV with ABV seems to be related, at least in part, to functional cardiac alterations secondary to stress-induced NOR release. As a consequence, cardiological monitoring of patients who are victims of multiple bee stings is recommended, together with a judicious evaluation of therapy involving drugs with a sympathomimetic action.

Can isolated myocardial bridging of the left anterior descending coronary artery be associated with sudden death during exercise?

A 38-year-old Caucasian man collapsed while playing tennis. There was no previous history of cardiac disease. At autopsy, myocardial bridging of the left anterior descending coronary artery was found without any other disease. Whether an isolated myocardial bridge may lead to a fatal cardiac event is a matter to be clarified.

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.

Causes of death in renal transplant recipients: a study of 102 autopsies from 1968 to 1991.

A study was conducted on 102 patients submitted to renal transplant who died and were autopsied at the University Hospital, Faculty of Medicine of Ribeirão Preto, Brazil, from 1968 to 1991. The cause of death, based on a review of medical records and autopsy reports, was assigned to one of the following categories: infectious (69.6%); cardiovascular (12.7%); gastrointestinal (7.8%); graft rejection (6.9%); tumoral (2.0%); and undetermined (1.0%). Among the 71 cases of death caused by infection, 28 (39.4%) showed disseminated agents involving two or more organs. Isolated pneumonia involved 17 patients (23.9%), followed by acute pyelonephritis in the transplanted kidney in 10 patients (14.1%). The most frequent agents were: bacteria (58.0%), divided into 'non-classified' (83.0%), Nocardia (10.6%) and Mycobacterium (6.4%); fungi (27.5%) represented by Cryptococcus (22.7%), Aspergillus, Candida and Pneumocystis carinii (18.1% each), Histoplasma (13.6%), Mucor and Paracoccidioides brasiliensis (4.5% each); viruses (6.2%) represented by Herpes simplex (60.0%); metazoa (5.0%, S. stercoralis), and protozoa (2.5%, T. cruzi). Cytomegalovirus (CMV) was identified in the lungs of 12 patients and was not directly correlated with death but was associated with other agents. In conclusion, immunodepressed patients such as renal transplant recipients should be carefully monitored for infection due to the high mortality rate.