Adverse effects of neonatal hypothyroidism on Wistar rat spermatogenesis

The effect of neonatal hypothyroidism on spermatogenesis was studied in Wistar rats of different age groups. Hypothyroidism was induced in newborn male rats from day one postpartum up to day 60 postpartum by daily administration of 0.05% methimazole (MMI) to the nursing mothers or directly through drinking water. The animals were killed at days 10, 15, 30, 40, and 60 postpartum, blood plasma was collected, and testes, epididymides, prostates, and seminal vesicles were separated and weighed. Testes were fixed in formalin for histological studies. Plasma testosterone (T), estradiol (E2), and sex hormone binding globulin (SHBG) were measured by radioimmunoassay. Hypothyroidism significantly reduced seminiferous tubule and lumen diameter. Control rats showed active spermatogenesis whereas in hypothyroid rats, the proliferation and differentiation of germ cells were arrested and their number was decreased. Plasma T, E2, and SHBG levels were significantly decreased at all ages for hypothyroid rats. The absolute weight of testes was decreased irrespective of age (except day 10 postpartum), however ventral, dorsolateral prostate, and epididymis weights were decreased at 30, 40, and 60 days postpartum. Coagulating gland weight was decreased in all age groups of hypothyroid rats. Hypothyroid rats of day 40 and 60 postpartum showed a decrease in absolute seminal vesicle weight. Relative testicular weights of hypothyroid rats decreased by postpartum day 15, 30, 40, and 60 whereas the opposite effect was observed by postpartum day 10. Relative organ weights were increased in epididymides (day 15 and 30 postpartum), seminal vesicles (day 30 and 40 postpartum), and dorsolateral prostates (day 15, 30, and 40 postpartum) and decreased in 10 and 60 day old hypothyroid rat.Ventral prostate relative weight was decreased in 40 and 60 day old rats. Th coagulating gland weight was decreased in 10, 15, and 60 days postpartum and an opposite effect was observed in 30 and 40 days hypothyroid rats. The present study clearly indicates that hypothyroidism adversely affects spermatogenesis; it also indicates that thyroid hormones are essential for normal spermatogenesis. Their effect may either be direct or indirect.     

Effect of shared care on blood pressure in patients with chronic kidney disease: a cluster randomised controlled trial

Background

Chronic kidney disease (CKD) is highly prevalent in patients with diabetes or hypertension in primary care. A shared care model could improve quality of care in these patients

Aim

To assess the effect of a shared care model in managing patients with CKD who also have diabetes or hypertension.

Design and setting

A cluster randomised controlled trial in nine general practices in The Netherlands.

Method

Five practices were allocated to the shared care model and four practices to usual care for 1 year. Primary outcome was the achievement of blood pressure targets (130/80 mmHg) and lowering of blood pressure in patients with diabetes mellitus or hypertension and an estimated glomerular filtration rate (eGFR)<60ml/min/1.73m².

Results

Data of 90 intervention and 74 control patients could be analysed. Blood pressure in the intervention group decreased with 8.1 (95% CI = 4.8 to 11.3)/1.1 (95% CI = −1.0 to 3.2) compared to −0.2 (95% CI = −3.8 to 3.3)/−0.5 (95% CI = −2.9 to 1.8) in the control group. Use of lipid-lowering drugs, angiotensin-system inhibitors and vitamin D was higher in the intervention group than in the control group (73% versus 51%, 81% versus 64%, and 15% versus 1%, respectively, [P = 0.004, P = 0.01, and P = 0.002]).

Conclusion

A shared care model between GP, nurse practitioner and nephrologist is beneficial in reducing systolic blood pressure in patients with CKD in primary care.     

New abnormalities in the morphology, cell surface receptors, and electrolyte metabolism of In(Lu) erythrocytes

The In(Lu) phenotype is inherited as an autosomal dominant trait and is characterized by suppression of the Lutheran, P1, i, and Aua erythrocyte blood group antigens. We have developed a monoclonal antibody (L21) that strongly agglutinates all erythrocytes except In(Lu), and we have identified eight In(Lu) individuals among 42,000 blood donors tested. Studies of two families confirmed the dominant mode of inheritance and revealed several new features of this phenotype. The erythrocytes of all five affected individuals from the two families exhibited diminished hemagglutination by the lectin concanavalin A, although they reacted normally with several other lectins. The erythrocytes of two affected individuals in one family exhibited marked acanthocytosis. The erythrocytes of the proposita of the other family exhibited a mild degree of poikilocytosis, but the cells of the other two affected individuals in this family had normal morphology. The osmotic fragility of fresh In(Lu) erythrocytes was normal, but after incubation for 24 hours at 37 degrees C in plasma the In(Lu) cells exhibited a marked increase in resistance to osmotic lysis. During the incubation period the erythrocytes lost K+ and their total cation content was diminished. These data indicate that in addition to the suppression of blood group antigens noted previously, the In(Lu) phenotype includes a variety of morphological abnormalities and a defect in electrolyte metabolism. The use of L21 and similar monoclonal antibodies provides a more sensitive means of detecting In(Lu) erythrocytes than typing with human anti-Lub antisera.     

The Relationship Between Nocturnal Blood Pressure and Hemorrhagic Stroke in Chinese Hypertensive Patients

To study the relationship between nocturnal blood pressure (BP) variation and spontaneous intracerebral hemorrhage (ICH) among Chinese hypertensive patients and its clinical significance, the authors retrospectively screened 371 patients with primary hypertension (189 patients with ICH, 182 patients without ICH) in Shanghai and analyzed their demographics, clinical information, nocturnal blood pressure variability and medication. Compared with the control group, the levels of blood glucose, triglycerides, and creatinine were significantly increased in the ICH group, along with a marked reduction in nocturnal BP drop (P<.05). Multivariate logistic regression indicated that blood glucose, creatinine, and nocturnal mean arterial pressure were risk factors for ICH, and the magnitude of nocturnal BP drop was negatively related to the risk for ICH. There was no significant difference in the prevalence of reverse dippers between the large hematoma volume group and the small hematoma volume group (χ²=2.529, P=.112), nor among the patients taking angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers, or calcium channel blockers (χ²=1.981, P=.371). Reverse dipping is associated with the risk for ICH, suggesting that appropriate antihypertensive drug and chronotherapy might be effective to normalize the rhythm of abnormal circadian variation in hypertensive patients.     

Elevated Serum Uric Acid is Associated With Angiotensinogen in Obese Patients With Untreated Hypertension

This study investigated the correlation between elevated serum uric acid (SUA) and angiotensinogen in obesity patients with hypertension. A total of 162 obese and 162 nonobese men with hypertension were recruited in this study. Plasma angiotensinogen levels were measured by enzyme‐linked immunosorbent assay. Fasting insulin (FINS) was evaluated by radioimmunoassay. Compared with nonobese patients, obese patients exhibited higher levels of angiotensinogen, FINS, and homeostasis model assessment index‐insulin resistance (HOMA‐IR) (P<.001 for all). Moreover, these indexes significantly increased in obese patients in the highest tertile of SUA when compared with those in the lowest tertile of SUA (P<.001, P=.002, P=.007, respectively). In the obese group, SUA levels were significantly related to angiotensinogen, FINS, and HOMA‐IR, respectively. Furthermore, it was demonstrated that obesity × uric acid was an independent contributor to angiotensinogen (β=0.257, P<.001). In conclusion, elevated SUA is strongly related to angiotensinogen in an obesity‐dependent manner in hypertension.     

Calcium Channel Blocker Compared With Angiotensin Receptor Blocker for Patients With Hypertension: A Meta‐Analysis of Randomized Controlled Trials

To explore the clinical effects of a calcium channel blocker compared with an angiotensin II receptor blocker in hypertensive patients, the authors collected data from randomized controlled trials. The pooled outcomes were all‐cause mortality, stroke, myocardial infarction, and heart failure. Eight head‐to‐head trials enrolling 25,084 patients were included. There was no significant mortality difference in the two arms (relative risk, 0.99; 95% confidence interval, 0.91–1.07). However, calcium channel blockers were more effective in reducing stroke (relative risk, 0.87; 95% confidence interval, 0.76–0.99) and myocardial infarction incidence (relative risk, 0.86; 95% confidence interval, 0.76–0.98). There was no significant difference with heart failure incidence between the two arms but a lower trend in patients with angiotensin II receptor blockers was noted (relative risk, 1.4; 95% confidence interval, 0.99–1.98). The meta‐analysis suggested that initially use of a calcium channel blocker might be superior to an angiotensin II receptor blocker for prevention of stroke and myocardial infarction.