Regulation of catecholamines by sustained and intermittent hypoxia in neuroendocrine cells and sympathetic neurons

Chronic intermittent hypoxia, a characteristic feature of sleep-disordered breathing, induces hypertension through augmented sympathetic nerve activity and requires the presence of functional carotid body arterial chemoreceptors. In contrast, chronic sustained hypoxia does not alter blood pressure. We therefore analyzed the biosynthetic pathways of catecholamines in peripheral nervous system structures involved in the pathogenesis of intermittent hypoxia-induced hypertension, namely, carotid bodies, superior cervical ganglia, and adrenal glands. Rats were exposed to either intermittent hypoxia (90 seconds of room air alternating with 90 seconds of 10% O2) or to sustained hypoxia (10% O2) for 1 to 30 days. Dopamine, norepinephrine, epinephrine, dihydroxyphenylacetic acid, and 5-hydroxytyptamine contents were measured by high-performance liquid chromatography. Expression of tyrosine hydroxylase and its phosphorylated forms, dopamine beta-hydroxylase, phenylethanolamine N-methyltransferase, and GTP cyclohydrolase-1 were determined by Western blot analyses. Both sustained and intermittent hypoxia significantly increased dopamine and norepinephrine content in carotid bodies but not in sympathetic ganglia or adrenal glands. In carotid bodies, both types of hypoxia augmented total levels of tyrosine hydroxylase protein and its phosphorylation on serines 19, 31, 40, as well as levels of GTP cyclohydrolase-1. However, the effects of intermittent hypoxia on catecholaminergic pathways were significantly smaller and delayed than those induced by sustained hypoxia. Thus, attenuated induction of catecholaminergic phenotype by intermittent hypoxia in carotid body may play a role in development of hypertension associated with sleep-disordered breathing. The effects of both types of hypoxia on expression of catecholaminergic enzymes in superior cervical neurons and adrenal glands were transient and small.     

Face-selective activation in a congenital prosopagnosic subject

Congenital prosopagnosia is a severe impairment in face identification manifested from early childhood in the absence of any evident brain lesion. In this study, we used fMRI to compare the brain activity elicited by faces in a congenital prosopagnosic subject (YT) relative to a control group of 12 subjects in an attempt to shed more light on the nature of the brain mechanisms subserving face identification. The face-related activation pattern of YT in the ventral occipito-temporal cortex was similar to that observed in the control group on several parameters: anatomical location, activation profiles, and hemispheric laterality. In addition, using a modified vase-face illusion, we found that YT's brain activity in the face-related regions manifested global grouping processes. However, subtle differences in the degree of selectivity between objects and faces were observed in the lateral occipital cortex. These data suggest that face-related activation in the ventral occipito-temporal cortex, although necessary, might not be sufficient by itself for normal face identification.     

Regulatory disorders in Israeli infants: epidemiologic perspective

The concept of regulatory disorders has been clinically defined. However, epidemiologic validity has not yet been investigated. Children between the ages of 6 and 36 months (N = 450) were included in the study. Two age groups were analyzed separately: 6 to 17 months (53%) and 18 to 36 months (47%). A specially designed questionnaire in Arabic and Hebrew pertaining to the physiologic and behavioral aspects of regulatory disorders was administered at the mother and child health clinics in northern Israel. It was established in the present study that a minimum of four regulatory items should be reported for the diagnosis of a regulatory disorder, as perceived by parents. Factor analysis revealed 6 and 10 different aggregates of regulatory items in the young and older age groups, respectively. The general prevalence of regulatory disorder as defined in the present study was found to be 18%. Age, maternal education, and sex were found to be significantly related to the prevalence of regulatory disorders. No difference in the prevalence of regulatory disorders between Arab and Jewish infants was found. Further validations of the concept of regulatory disorder as well as devising appropriate measurements in well-designed studies are warranted.     

Forecasting the In Vivo Performance of Four Low Solubility Drugs from Their In Vitro Dissolution Data

Purpose. To assess the usefulness of biorelevant dissolution tests in predicting food and formulation effects on the absorption of four poorly soluble, lipophilic drugs. Methods. Dissolution was studied with USP Apparatus II in water, milk, SIF_sp, FaSSIF, and FeSSIF. The in vitro dissolution data were compared on a rank order basis with existing in vivo data for the tested products under fasted and fed state conditions. Results. All drugs/formulations showed more complete dissolution in bile salt/lecithin containing media and in milk than in water and SIF_sp (USP 23). Comparisons of the in vitro dissolution data in biorelevant media with in vivo data showed that in all cases it was possible to forecast food effects and differences in absorption between products of the same drug with the physiologically relevant media (FaSSIF, FeSSIF and milk). Differences between products (both in vitro or in vivo) were less pronounced than differences due to media composition (in vitro) or dosing conditions (in vivo). Conclusions. Although biorelevant dissolution tests still have issues which will require further refinement, they offer a promisingin vitro tool for forecasting the in vivo performance of poorly soluble drugs.     

Orthodontic space closure of lost traumatized anterior teeth – case report

Abstract – This case report refers to an 11‐year‐old boy with avulsion of the upper left central and lateral incisors. The teeth were replanted after 4 h, splinted with a semi‐rigid splint for 12 days, and then endodontically treated. Severe progressive root resorption was seen after 2 years and the teeth were extracted. The boy had a normal occlusion with spacing in both jaws and slight protrusion of the anterior teeth. The treatment objectives were to close some of the spaces by mesial movement of the buccal segments in the upper jaw to minimize bone loss for a future single osseointegrated implant. Fixed appliance in combination with a removable plate was used for the mesial movements, levelling, and alignment of the upper jaw. Fixed appliance in the lower jaw and Class II traction were used for the final adjustment of the occlusion. A good occlusion with coincident upper and lower midlines and up‐righted anterior teeth were achieved. A Maryland bridge was performed as a temporary solution for a future osseointegrated implant.     

Thromboembolic Events Following Splenectomy: Risk Factors,Prevention, Management and Outcomes

Background

Thromboembolic events following splenectomy are not uncommon. However, the role of thromboprophylaxis and risk factors for thrombosis, as well as the clinical course and outcomes, are not well characterized.

Methods

A retrospective review of individuals who underwent splenectomy between January 2006 and December 2015 in two university hospitals.

Results

Overall, 297 patients underwent splenectomy [open splenectomy (n = 199), laparoscopic splenectomy (n = 98)]. Mechanical (thigh-length pneumatic compression stockings) and pharmacologic thromboprophylaxis (40 mg enoxaparin daily, starting 12 h after surgery until discharge) was provided for all patients. One hundred and sixteen patients (39%) also received an extended thromboprophylaxis course of enoxaparin for 2–4 weeks after discharge. Twenty-three patients (7.7%) experienced thrombotic complications following splenectomy, including 16 cases (5.4%) of portal-splenic mesenteric venous thrombosis (PSMVT), 5 (1.7%) pulmonary embolism and 2 (0.7%) deep vein thrombosis. Longer operative time (mean operative time of 405 vs. 273 min, P = 0.03) was independently associated with PSMVT. Post-splenectomy thrombocytosis was not associated with thrombosis (P = 0.41). The overall thrombosis rate was significantly lower in patients who received an extended thromboprophylaxis course following splenectomy (3.4 vs. 10.5%, P = 0.02). Complete resolution of thrombosis was observed in most cases (n = 20, 87.0%), with no recurrent thrombosis during a mean follow-up of 38 ± 25 months.

Conclusions

Thromboembolic complications, mainly PSMVT, are common following splenectomy. Longer operative time was associated with thrombosis. Significantly lower rates of thrombosis were found in patients who received an extended thromboprophylaxis course.

     

Association between maternal depression and maternal sensitivity from birth to 12 months: a meta-analysis

Maternal sensitivity plays a central role in shaping children’s development across a number of domains, and may be disrupted by depression. The current meta-analysis quantified the magnitude of the association between depression and maternal sensitivity, defined broadly as timely, contingent, and appropriate responding to infants’ cues, from birth to 12 months. Across k = 48 studies and n = 4,934 mother–infant dyads, the aggregate effect size between depression and maternal sensitivity was r = ?.16, p < .0001, indicating that mothers with higher depression levels were less sensitive than mothers with lower depression levels. Studies that compared a depressed group with a nondepressed/control group had larger effect sizes (r = ?.35, p < .0001) than studies that examined depression within a single sample of either unselected cases or clinical-only cases (r = ?.11, p < .001), suggesting that clinical levels of depression may pose a particular threat to sensitive parenting. Clinical implications (e.g. screening, prevention) are discussed.     

In vivo effect of dried chicory root (Cichorium intybus L.) on xenobiotica metabolising cytochrome P450 enzymes in porcine liver

Cytochrome P450 (CYP) enzymes are widely studied for their involvement in metabolism of drugs and endogenous compounds. In porcine liver, CYP1A2, 2A and 2E1 are important for the metabolism of skatole. Feeding chicory roots to pigs is known to decrease the skatole concentration in plasma and fat. In the present study we investigated the effect of chicory on CYP mRNA and protein expression, as well as their activity. Male pigs were feed dried chicory root for 16 days before liver samples were collected. By the use of RT-PCR and Western blotting we showed that the mRNA and protein expression of CYP1A2 and 2A were increased in chicory fed pigs. The mRNA expression of CYP2E1 was increased, while there was no effect on protein expression. Activity of CYP1A2 and 2A were increased in chicory feed pigs; this was not the case for CYP2E1 activity. In conclusion; oral administration of chicory root for 16 days to pigs increased the mRNA expression of CYP1A2, 2A and 2E1; and the protein expression of CYP1A2 and 2A. The activities of CYP1A2 and 2A were increased.