The GnRH system of seasonal breeders: anatomy and plasticity

Seasonal breeders, such as sheep and hamsters, by virtue of their annual cycles of reproduction, represent valuable models for the study of plasticity in the adult mammalian neuroendocrine brain. A major factor responsible for the occurrence of seasonal reproductive transitions is a striking change in the responsiveness of gonadotropin-releasing hormone (GnRH) neurons to the inhibitory effects of gonadal steroids. However, the neural circuitry mediating these seasonal changes is still relatively unexplored. In this article, we review recent findings that have begun to define that circuitry and its plasticity in a well-studied seasonal breeder, the ewe. Tract tracing studies and immunocytochemical analyses using Fos and FRAs as markers of activation point to a subset of neuroendocrine GnRH neurons in the MBH as potential mediators of pulsatile GnRH secretion. Because the vast majority of GnRH neurons lack estrogen receptors, seasonal changes in responsiveness to estradiol are most probably conveyed by afferents. Two possible mediators of this influence are dopaminergic cells in the A14/A15 cell groups of the hypothalamus, and estrogen receptor-containing cells in the arcuate nucleus that project to the median eminence. The importance of GnRH afferents in the regulation of season breeding is underscored by observations of seasonal changes in the density of synaptic inputs onto GnRH neurons. Thyroid hormones may participate in this remodeling, because they are important in seasonal reproduction, influence the morphology of other brain systems, and thyroid hormone receptors are expressed within GnRH neurons. Finally, in the hamster, neonatal hypothyroidism affects the number of caudally placed GnRH neurons in the adult brain, suggesting that thyroid hormones may influence development of the GnRH system as well as its reproductive functions in the adult brain.     

Sodium ramping in hemodialysis: a study of beneficial and adverse effects

Sodium ramping has been introduced as a technique to decrease side effects occurring during hemodialysis. We studied sodium ramping in 414 dialysis sessions in 23 patients by randomizing 2-week blocks of dialysis to either steady dialysate sodium of 140 mEq/L, linear sodium ramping during dialysis from 155 mEq/L to 140 mEq/ L, or stepwise ramping (sodium of 155 mEq/L for 3 hours and 140 mEq/L for 1 hour). We studied the number and severity of hypotensive and hypertensive episodes. A hypotensive episode was defined as an abrupt decline of systolic blood pressure of more than 50 mm Hg, a decrease in blood pressure accompanied by symptoms requiring intervention, or systolic blood pressure of less than 90 mm Hg even without symptoms. A hypertensive episode was defined as a sudden increase in systolic blood pressure of over 30 mm Hg. We also recorded other side effects (headache, cramps, nausea, vomiting, dizziness, thirst, fatigue, weight gain, and blood pressure) during, immediately after, and between dialysis sessions. There was no major difference between the two ramping protocols, but compared with standard dialysis, both decreased total number of side effects from 4.0 to 3.0 (P = 0.057); the number of hypotensive episodes decreased from 1.3 to 0.7 (P = 0.036). The lowest blood pressure was 114/66 mm Hg during control and 123/69 mm Hg during ramping (P < 0.0001). The frequency of cramps during dialysis decreased from 0.9 to 0.5 (P = 0.006). There was no difference in headache, nausea, or vomiting. The number of hypertensive episodes increased from 0.045 to 0.086 during ramping (P = 0.125). Of 23 patients, only five (22%) had a marked decrease in symptoms; two of the three most symptomatic patients showed no significant improvement. Between dialysis sessions, patients complained of more fatigue and thirst (P < 0.0001 and P = 0.0028, respectively), and interdialytic weight gain following ramping was 5.1% of body weight compared with 4.4% without ramping (P < 0.0001). Blood pressure also increased following ramping, from 143/79 mm Hg to 152/81 mm Hg (P = 0.001). Ramping can decrease the overall number of side effects, but increases interdialytic symptoms, weight gain, and hypertension. In most instances, it simply changes the time the side effects occur. Only 22% of patients have significant benefit. These patients can be identified only through trial and error, as no model of these patients can be created.     

Doppler ultrasonographic evaluation of blood flow in the superior mesenteric artery in celiac patients and in healthy controls in fasting conditions and after saccharose ingestion

We studied, by means of Doppler ultrasonography, the blood flow in the superior mesenteric artery in 12 untreated patients with celiac disease (nontropical sprue) and in 15 healthy controls; peak systolic velocity, end diastolic velocity, mean velocity, flow volume, and resistive index were measured in the fasting state and at regular intervals after ingestion of 0.5 liter of water containing 50 g of saccharose. Under fasting conditions, celiac patients showed peak systolic velocity, end diastolic velocity, mean velocity, and flow volume values significantly higher than those of normal subjects, whereas resistive index was significantly lower. After saccharose ingestion these parameters showed greater variations in normal subjects than in celiac patients. Fasting end diastolic velocity turned out to be the best parameter to distinguish celiac patients from healthy subjects. Doppler ultrasonography of the superior mesenteric artery could discriminate between normal subjects and celiac patients with overt disease. However, these data need further confirmation given the limited sample that we studied; moreover, the capability of this technique in distinguishing nontropical sprue from other gastrointestinal diseases that cause increasing splanchnic flow remains to be ascertained.     

Induction of proinflammatory cytokine and antioxidant enzyme gene expression following brief myocardial ischaemia

PURPOSE: In a recent study we found an increased resistive index immediately after extracorporeal shock wave lithotripsy (ESWL) in patients older than 60 years, which suggests renovascular disturbance. The present 26-month followup study was undertaken to investigate the relevance of elevated resistive index levels and the incidence of new onset hypertension. MATERIALS AND METHODS: Of the initial 76 patients 57, including 20 of the 23 at risk patients 60 or greater years, group 3), were followed for more than 26 +/- 6 months after ESWL. Followup included 2 resistive index measurements by Doppler ultrasound of the treated and the contralateral kidney, at least 2 blood pressure measurements 1 week apart and excretory urography as well as determination of plasma renin activity in 9 patients. RESULTS: With 1 exception, elevated resistive index levels and hypertension were observed exclusively in patients older than 60 years. In these patients the resistive index ranged between 0.65 and 0.86 (mean plus or minus standard deviation 0.74 +/- 0.05, normal less than 0.7). This increase in resistive index was statistically significant (p < 0.0001). Compared to the levels obtained immediately after ESWL, the resistive index continued to increase in all 9 patients older than 60 years who had hypertension (45%), whereas in the normotensive patients the resistive index was either stable or decreased. There was a strong positive correlation (0.903) between pathological resistive index levels and blood pressure. CONCLUSIONS: Patients older than 60 years are at risk for disturbances of renal perfusion as assessed by the resistive index, and 45% of these patients have new onset hypertension within 26 months of treatment.     

Targeted overexpression of protein kinase C beta2 isoform in myocardium causes cardiomyopathy

Increased cardiovascular mortality occurs in diabetic patients with or without coronary artery disease and is attributed to the presence of diabetic cardiomyopathy. One potential mechanism is hyperglycemia that has been reported to activate protein kinase C (PKC), preferentially the beta isoform, which has been associated with the development of micro- and macrovascular pathologies in diabetes mellitus. To establish that the activation of the PKCbeta isoform can cause cardiac dysfunctions, we have established lines of transgenic mice with the specific overexpression of PKCbeta2 isoform in the myocardium. These mice overexpressed the PKCbeta2 isoform transgene by 2- to 10-fold as measured by mRNA, and proteins exhibited left ventricular hypertrophy, cardiac myocyte necrosis, multifocal fibrosis, and decreased left ventricular performance without vascular lesions. The severity of the phenotypes exhibited gene dose-dependence. Up-regulation of mRNAs for fetal type myosin heavy chain, atrial natriuretic factor, c-fos, transforming growth factor, and collagens was also observed. Moreover, treatment with a PKCbeta-specific inhibitor resulted in functional and histological improvement. These findings have firmly established that the activation of the PKCbeta2 isoform can cause specific cardiac cellular and functional changes leading to cardiomyopathy of diabetic or nondiabetic etiology.     

Carcinoid of the gallbladder. A report of a clinical case treated by video laparoscopic cholecystectomy

The authors report a clinical case of the gallbladder carcinoid tumour treated with laparoscopic cholecystectomy. After a short analysis of the classification, the malignant potentiality and the symptoms of gallbladder carcinoids, they conclude that it is possible to treat carcinoids with laparoscopic cholecystectomy, but only in some selected cases, that is to say in the absence of factors indicative of local invasion and that in the other cases it is preferable the classic surgical treatment of laparotomic resection.     

The routine sampling procedure for PKU should be changed. Venous puncture is less painful than heel lancing

All newborns in Sweden are screened for phenylketonuria (PKU), among other things, blood usually being sampled by heel lancing. Because it is unnecessarily painful, however, this form of sampling in newborns has recently been questioned. There is reason to recommend sampling from a dorsal hand vein as the method of choice for PKU screening purposes.     

Plasma GABA in children and adolescents with mood, behavior, and comorbid mood and behavior disorders: a preliminary study

Plasma GABA concentrations (pGABA) were measured in 115 inpatients (aged 7-17) with child psychiatric disorders. Group mean pGABAs were compared for 38 patients with mood disorders only (MOOD), 29 with behavior disorders only (BEH), 48 with comorbid mood and behavior disorders (MOOD + BEH), and 14 normal controls (CON, aged 14-17). The BEH group was characterized by (a) high mean pGABAs (157 vs. 133 pmol/ml), (b) lower mean pGABAs in BEH subjects who had been receiving pharmacotherapy with SSRIs or other medications (p < 0.026), and (c) decreased pGABA with increasing age (p = 0.019). These features were not found in controls or in groups of patients with mood disorders (MOOD or MOOD + BEH). Elevated mean pGABA in the BEH group appeared specifically in patients with comorbid CD and ADHD, not in patients with ADHD or CD alone (p = 0.004). No patient in BEH (or CON) had pGABA below 100 pmol/ml, but low pGABAs were found in 15% of MOOD patients (who had no behavior disorder) and in 16% of MOOD + BEH patients. Pharmacotherapy did not change pGABAs in the MOOD or the MOOD + BEH groups. No pGABA differences were found among the anxiety disorders, either alone or with mood or behavior comorbidity. The finding that plasma GABA levels are elevated in nonmedicated behavior disorders that present in the absence of mood disorders, and appear to lower following medication treatments, merits increased attention to the pharmacological study of nonaffective behavior disorders.