Alterations in the ultrastructure of cardiac autonomic nervous system triggered by crotoxin from rattlesnake (Crotalus durissus cumanensis) venom.

This study explored the toxic effects of crotoxin isolated from Crotalus durissus cumanensis venom on the ultrastructure of mice cardiac autonomic nervous system. Mice were intravenously injected with saline (control group) and crotoxin diluted in saline venom (study group) at a dose of 0.107 mg/kg mouse body weight. Samples from the inter-ventricular septum were prepared for electron microscopy after 6 h (G1), 12 h (G2), 24 h (G3) and 48 h (G4). The G1 group showed some cardiomyocyte with pleomorphic mitochondria. Capillary swollen walls, nerve cholinergic endings with depleted acetylcholine vesicles in their interior and other depletions were observed. A space completely lacking in contractile elements was noticed. The G2 group demonstrated a myelinic figure, a subsarcolemic region with few myofibrils and nervous cholinergic terminal with scarce vacuoles in their interior. The G3 group demonstrated a structure with a depleted axonic terminal, mitochondrias varying in size and enhanced electron density. In addition, muscular fibers with myofibrillar structure disorganization, a depleted nervous structure surrounded by a Schwann cell along with an abundance of natriuretic peptides, were seen. An amyelinic terminal with depleted Schwann cell and with scarce vesicles was also observed. Finally, axonic lysis with autophagic vacuoles in their interior and condensed mitochondria was observed in the G4 group. This work describes the first report of ultrastructural damage caused by crotoxin on mice cardiac autonomic nervous system.     

Biotin deficiency in protein-energy malnutrition

Several of the clinical and biochemical manifestations of biotin deficiency also occur in severe protein-energy malnutrition (PEM). Average plasma biotin concentrations were lower in 16 malnourished children (10 with marasmus, 3 with kwashiorkor and 3 with marasmic kwashiorkor) than in 31 controls. Lymphocyte mitochondrial carboxylase activities were studied in 11 controls and in 10 patients with PEM; on the average, they were lower in the patients. Their activation indices (the ratio of enzyme activity in cells incubated with biotin to activity in cells incubated without the vitamin) were higher in PEM. All these differences were statistically significant. None of these parameters were age-dependent in a range between 3 and 72 months. Carboxylase activities and plasma biotin levels increased to normal during nutritional recovery in two malnourished patients who were further studied. These results suggest that there is biotin deficiency in severe PEM. Urinary biotin concentrations, expressed per g of creatinine, were higher in the patients than in the controls; this may have been caused by increased renal clearance or by the reduced creatinine excretion which occurs in malnourished individuals. It will be important in future studies to determine the relative contribution of biotin deficiency to the malnourished phenotype.     

Chronic cyclosporin A nephrotoxicity, P-glycoprotein overexpression, and relationships with intrarenal angiotensin II deposits.

P-glycoprotein (P-gp) expels hydrophobic substances from the cell, including chemotherapeutic agents and immunosuppressants such as cyclosporin A (CsA) and FK506. Exposure of cultured renal tubular cells to CsA induces P-gp overexpression in cell membranes. Angiotensin II has recently been implicated as the principal factor responsible for progression of interstitial fibrosis induced by CsA. To investigate the in vivo relationships between histological lesions, P-gp overexpression, and intrarenal angiotensin II deposits, we developed a model of chronic CsA toxicity in Sprague-Dawley rats treated with 25 mg/kg/day CsA for 28 and 56 days and fed either a standard maintenance diet or a low-salt diet. Immunohistochemical methods were used to study the expression of P-gp in renal tubular cells and the appearance of intrarenal angiotensin II deposits. Rats treated with CsA developed chronic nephrotoxicity lesions that were more evident in the group fed the low-salt diet. Treatment with CsA induced overexpression of P-gp in tubular cells of the kidney that increased with time. We found that immunohistochemical expression of P-gp was slightly more severe in rats fed a low-salt diet. Intrarenal deposits of angiotensin II were more evident in rats treated with CsA; these deposits also increased with time. This finding was also more relevant in rats given the low-salt diet. The up-regulation of P-gp was inversely related to the incidence of hyaline arteriopathy (r = -0.65; P < 0.05), periglomerular (r = -0.58; P < 0.05) and peritubular fibrosis (r = -0.63; P < 0.05), and intrarenal angiotensin H deposits in animals with severe signs of nephrotoxicity (r = -0.65; P < 0.05). These results support the hypothesis that the role of P-gp as a detoxicant in renal cells may be related to mechanisms that control the cytoplasmic removal of both toxic metabolites from CsA and those originating from the catabolism of signal transduction proteins (methylcysteine esters), which are produced as a result of ras activation in presence of angiotensin II.     

A new syndrome characterized by mental retardation, epilepsy, palpebral conjunctival telangiectasias and IgA deficiency

Mental retardation, epilepsy, palpebral conjunctival telangiectasias and diminished serum IgA, with a particular facies and shortened fifth finger were found in a 12-year-old Mexican girl. She has six siblings, of whom five have the same characteristics. The parents and the elder sister were not affected, and there was no history of consanguinity. This seems to be a new syndrome, and as both sexes are affected, the parents are normal and several siblings have the same syndrome, we postulate an autosomal recessive mode of inheritance.     

Unusual inheritance of Becker type muscular dystrophy.

A family with Becker type muscular dystrophy is described, in which two females were severely affected, giving the family tree the appearance of dominant inheritance.     

Preoperative versus postoperative adjuvant radiotherapy for surgically curable carcinoma of the rectum and distal sigmoid colon

From January 1979 to October 1986, 86 patients with surgically resectable adenocarcinoma of the rectum or rectosigmoid were treated with adjuvant radiotherapy consisting of preoperative 2,400 cGy (22 patients), preoperative 4,000 cGy (14 patients), "sandwich" technique (27 patients), and postoperative irradiation (23 patients). Average follow-up was 42.9 months. The local recurrence rate was 4.5%, 9.1%, 7.4%, and 34.8%, respectively. The distant metastasis rate was 18.2%, 18.2%, 7.4%, and 30.4%, respectively. Preoperative radiotherapy with adequate surgical resection appears more effective in reducing the incidence of local recurrence.     

Nonpuerperal breast infection

Objective: We undertook a microbiological study of purulent specimens from women with symptomatic breast abscesses.Methods: Fifty-one purulent samples were collected in 2 periods (December 1991-April 1992 and January 1994-June 1994) from nonpuerperal breast abscesses in 44 patients attending our hospital.Results: One of the most frequently isolated microorganisms was Proteus mirabilis (9 patients, 20.4%), present as a pure culture in all but 1 specimen (isolated together with Peptostreptococcus spp.). Staphylococcus aureus was isolated in 10 specimens, 6 of which were post-tumorectomy abscesses. Polymicrobial anaerobic flora were isolated in 11 specimens (21.5%); Staphylococcus epidermidis in 4 (8%); and Streptococcus milleri,Alcaligenes sp., and mixed aerobic-anaerobic flora in 1 specimen each. The 7 remaining samples (13.7%) were negative bacteriological cultures.Conclusions: We draw attention to the frequent isolation of P. mirabilis in recurrent and torpid breast abscesses in 4 women in whom surgery was necessary in addition to antibiotic treatment.     

Liver ultrastructural pathology in mice envenomed with Uracoan rattlesnake (Crotalus vegrandis) venom

In South America rattlesnake venom activities have not been entirely characterised. Some studies have shown haemorrhagic, myotoxic, and neurotoxic effects as manifestations of envenoming in experimental animals and humans. Biopsy specimens were obtained from liver and immediately fixed in situ and observed in Hitachi H-500 and H-7100 electron microscopes. In this work the ultrastructural analysis of experimental mice liver showed hepatocytes with increased lipid droplets content and significant vacuolation in areas of their cytoplasm limiting with the Disse space. Lysosomes and altered peroxisomes exhibiting a very dense electron content were also evident. Mitochondrial pleomorphism including cup-shaped and ring-shaped mitochondria were frequently found. The cristae were scarce or absent in the majority of mitochondria observed. The rough endoplasmic reticulum showed a preferentially disposition lining the outer mitochondrial membranes. In some section glycogen particles were scarce and lipofuchsin granules could be observed. Red blood cells showed endothelial cell adherence and, in many instances, the liver sinusoids were observed plugged with aggregated red blood cells. In conclusion, using an animal model that probably correlates well with the pathological effects found in envenomed humans, we have shown the severe hepatocellular alterations caused by this venom.     

Ropivacaine

This paper describes the pharmacological, pharmacokinetic and pharmacodynamic features of ropivacaine on both an experimental and clinical level. Ropivacaine is an amide-type local anesthetic whose chemical structure is related to that of mepivacaine and bupivacaine and whose duration of effect falls between the two. Ropivacaine is a less potent effector of motor blockade than bupivacaine, and its toxic effects on the central nervous system and myocardial tissue is likewise less. Ropivacaine has been employed for epidural anesthesia and analgesia (including through a caudal approach), for peripheral motor blockade, for local infiltration (in gel form), and for intravenous regional anesthesia in ophthalmologic surgery involving peri- and retrobulbar blockade. Subarachnoid use has not yet been accepted in Spain, although phase IV clinical trials of this application have begun. Concentrations of 2 mg/ml (0.2%) and 7.5 mg/ml (0.75%) and 10 mg/ml (1%) are available in Spain.