Neonatal cholinergic lesions and development of exploration upon administration of the GABAa receptor agonist muscimol in preweaning rats

Neonatal rats were administered 192 IgG-saporin (192 IgG-Sap), a selective cholinergic immunotoxin, on postnatal day (PND) 7. Behavioural responsiveness to muscimol, a GABAa receptor agonist, was then assessed using locomotor activity and object exploration tests on PND 18. In Experiment 1, 192 IgG-Sap-lesioned and control rats were injected with the GABAa agonist, muscimol, on PND 18 and tested in a standard open field test. Muscimol reduced rearing responses in both control and 192 IgG-Sap-lesioned animals whereas reduced wall-rearing responses occurred in control animals only. 192 IgG-Sap also reduced rearing and wall-rearing responses. In Experiment 2, muscimol effects were evaluated on PND 18 in a spatial open field test in which object exploration in addition to locomotion and rearing responses was assessed. Neonatal cholinergic lesion per se increased locomotion during object exploration while decreasing time spent exploring objects. Depressant effects of muscimol on object exploration were also evident. As a whole, these data provide evidence for (i) basal forebrain (BF) cholinergic control on locomotor activity and object exploration and (ii) GABAa-mediated regulation of selective behavioural patterns associated with locomotion and exploration in weaning rats. Neonatal cholinergic lesions, however, do not appear to alter reactivity to GABAergic agonists in juvenile rats.     

Cross-sectional and prospective data on urinary calcium and urinary stone disease

BACKGROUND: Urinary calcium is considered a risk factor for urinary stone disease (USD), although prospective data are missing. This epidemiologic study investigates cross-sectionally and longitudinally the relation of urinary calcium excretion to USD. METHODS: In the Gubbio Population Study, data on USD were collected by questionnaire during medical examinations from 1989 to 1992 (baseline) and telephone interviews in 1997 to 1998 (follow-up). Baseline data collection included overnight urinary calcium excretion and use of medications. Study cohort was made of 1458 men and 1799 women, age 25 to 74 years, and not on treatment with diuretics at baseline. USD was diagnosed by: excretion of stone(s), and/or radiographic or ultrasonic evidence, and/or surgical or endoscopic removal of stone(s). RESULTS: At baseline, urinary calcium excretion was higher in persons with than without USD (215 and 182 micromol/hour, P < 0.001) and related to USD prevalence independent of gender, age, and other variables (P < 0.001). Among persons without USD at baseline, baseline urinary calcium excretion was higher in persons with than without incident USD at follow-up (202 and 181 micromol/hour, P = 0.034) and related to incident USD independent of gender, age, and other variables. A difference of 100 micromol/hour (about 1 SD) in urinary calcium excretion related to a difference in USD risk of 1.32 for prevalence and 1.21 for incidence (95% CI = 1.15/1.52 and 1.01/1.45, respectively) in multivariate analyses controlled for gender, age, body mass index, parental history of USD, urinary excretion of urea, sodium, and potassium. CONCLUSION: Cross-sectional and prospective data show that urinary calcium excretion is a risk factor for USD.     

Familial Sneddon's syndrome

A syndrome associating Livedo Reticularis (LR) with Cerebrovascular disease (CVD) was described, in 1965, by Sneddon. It occurs sporadically, but a few familial cases of Sneddon's Syndrome (SS) have been reported, like these 3 cases that represent one of the largest number among siblings. We studied three male brothers, aged 28, 37 and 42 years, with CVD (ischaemic stroke in 2 patients and cerebral haemorrhages in the third) and their sister with no CVD. All patients presented with long lasting Livedo Reticularis, extending beyond the lower limbs. Skin biopsy on the centre of the reticular pattern showed, only in the second patient, partial endothelium detachment in dermo-hypodermic blood vessels. The males also had accesses of Livedoid Vasculitis (LV), in which a skin biopsy showed obliteration of several upper dermal vessels with hialin thrombi and a very scarce inflammatory infiltrate. Complementary studies, with an extensive investigation on pro-coagulation/pro-thrombotic features including antiphospholipid antibodies, were repeatedly negative. Their non-consanguineous parents were not affected, but among these kindred of 9 individuals, apart from the 4 patients reported above, LR and LV were present in two other brothers and also in an aunt and uncle, suggesting autosomal dominant pattern of inheritance, with incomplete penetrance. The relationship between Sneddon's Syndrome and Antiphospholipid Antibody Syndrome is controversial. The present cases, having repeatedly negative antiphospholipid antibodies, support the classification of Sneddon's Syndrome as an independent nosological entity.     

Gestational diabetes: universal or selective screening?

OBJECTIVE: To evaluate the incidence of gestational diabetes in our population and verify costs of universal screening. To assess neonatal and obstetrical outcomes with respect to maternal epidemiological characteristics. METHODS: Eight hundred and fifty-six pregnant women between 24th and 28th weeks of gestation were examined in this observational study. Universal screening with glucose challenge test was used to screen the group for gestational diabetes. History, obstetrical and neonatal outcomes were collected and then analyzed. RESULTS: Gestational diabetes was diagnosed in 6.6% of cases. Patients with at least one risk factor had a cesarean section in 50% of cases and a spontaneous vaginal delivery in 23.59% of cases (p < 0.001). The absence of any risk factor was found in 73.7% of positive glucose tolerance test and in 62.5% of affected patients. The cost of universal screening in our study, was 57,60 Euros per case identified. CONCLUSIONS: Given the high prevalence of diabetes, the high proportion of patients potentially not identified with a selective screening in this study and the relatively low cost, universal screening for gestational diabetes seems the best way to identify patients and prevent adverse obstetrical and neonatal outcomes.     

Microvessel damage by B. jararacussu snake venom: pathogenesis and influence on muscle regeneration.

The loss of muscle mass consequent to poor muscle regeneration is a common sequela following the injection of Bothrops jararacussu snake venom. Since an intact microvasculature plays a central role in the success of muscle regeneration, the poor muscle regeneration seen after envenomation could be explained by damage to the local microvasculature. In this work, we investigated the pathogenesis of microvessel damage caused by B. jararacussu venom and its correlation with poor muscle regeneration. The right soleus muscle of adult mice was injected with 80 microg of venom and the mice were killed from 2 min to 3 months later. Similarly, the soleus muscle of other mice was injected with 80 microg of bothrosptoxin-I (BthTX-I), a non-vasculotoxic myotoxin. Tissue samples were prepared for analysis by electron (venom only) and light (venom and BthTX-I) microscopy. The extent of revascularization was assessed using light microscopy by examining recanalization of thrombi and calculating the individual capillary-to-fiber-ratio, the number of capillaries around a fiber and the capillary/muscle cell ratio. Microvessel damage by venom started within 5 min and, after 6 h, there was total degeneration of the capillaries with failure of the local microcirculation. The time-course of the ultrastructural lesions suggested that endothelial cells were probably damaged by a direct action of B. jararacussu venom on these cells. The revascularization of muscle damaged by venom, but not by BthTX-I, occurred later and was very poor. These results indicate a central role for vascular lesions in muscle regeneration after damage by B. jararacussu venom.     

Chemotherapy plus Sequential Hormonal Therapy for Advanced and Recurrent Endometrial Carcinoma: A Phase II Study

We evaluated the therapeutic value of sequential cyclical hormonal therapy (megestrol acetate, and tamoxifen citrate) plus single-agent chemotherapy (carboplatin) in the outpatient management of advanced or recurrent endometrial cancer. Carboplatin (300 mg/m²) was administered every 4 weeks for six courses or until disease progression. In addition, patients alternated megestrol acetate (80 mg orally twice daily) with tamoxifen citrate (20 mg orally twice daily) every 3 weeks. Thirteen of 18 (72.2%) patients were considered evaluable. Four patients (30.8%) had a complete response, six (46.2%) had a partial response, one (7.7%) had stable disease, and two patients (15.4%) progressed. Six of seven patients with vaginal disease responded. The median progression-free interval was 14 months for complete responders. Two patients (15.4%) are alive with no evidence of disease at 41 and 59 months. Seven of 13 patients experienced a hematologic toxicity (six grade 2, one grade 3); all resolved within 2 weeks. Dose reduction of carboplatin to 200 mg/m²was required in one patient. No other toxicities were encountered. The median survival for all patients is 11 months, and is 33 months for complete responders. We conclude that a regimen of carboplatin plus sequential hormonal therapy shows promise in this pilot study for the treatment of advanced or recurrent endometrial cancer.     

Sequential fine needle aspiration biopsy in glomerulonephritis

Cellular immune mechanisms have been shown to play a prominent role in glomerulonephritis. Cellular mediators of inflammation cause both acute and progressive glomerular and tubular injury. Understanding the mediation pathways offers the opportunity for therapeutic manipulation. In addition to polymorphonuclear leucocytes, monocytes/macrophages, B-cells and T-cells subsets are being enumerated in normal and diseased renal tissues. The correlation between immunological findings in peripheral blood and infiltrate composition in renal tissue, by using weekly Fine Needle Aspiration Biopsy (FNAB), for assessing the clinical status and monitoring the immunosuppressive therapy was the aim of this study. When determining the intensity of inflammation the numerical values of the Total Corrected Increment (T.C.I.) were defined as follows: less than 1.5 no inflammation; from 1.5 to 2.0 inflammation possible; greater than 2.0 inflammation. The ratio between OKT4 and OKT8 was used as the index: greater than 2.0 immunologic activation; greater than 2.0 no immunologic activation. When the T.C.I. was greater than 1.5 and the OKT4/OKT8 less than 2.0, or the T.C.I. less than 1.5 and the OKT4/OKT8 greater than 2.0 we used only a standard treatment. When both activation indexes were in the normal range we have not treated the patients. When the T.C.I. was greater than 1.5 and the OKT4/OKT8 was greater than 2.0 we treated the patients with standard treatment plus methylprednisolone pulses every time the activation indexes monitored by FNAB, showed an increase. A spontaneous improvement was obtained in untreated patients. The patients treated by standard therapy alone showed a different outcome. All patients treated with standard therapy plus methyl-prednisolone pulses showed a progressive clinical improvement.(ABSTRACT TRUNCATED AT 250 WORDS)     

Discrimination between<Emphasis Type="Italic"> Theileria lestoquardi</Emphasis> and<Emphasis Type="Italic"> Theileria annulata</Emphasis> in their vectors and hosts by RFLP based on the 18S rRNA gene

Theileria lestoquardi and T. annulata can occur in similar vectors, and current available probes based on the 18S rRNA gene showed cross-reaction between the two species. However, we developed a species-specific RFLP test based on the MspI restriction enzyme, able to cut amplified products from T. lestoquardi only and to discriminate the two species in both tick and blood samples.