Systemic Glucose Regulation by a Hindbrain Inhibitory Circuit in a Mouse Model of Type 1 Diabetes.

INTRODUCTION: Previous work showed that increasing the electrical activity of inhibitory neurons in the dorsal vagal complex (DVC) is sufficient to increase whole-body glucose concentration in normoglycemic mice. Here we tested the hypothesis that deactivating GABAergic neurons in the dorsal hindbrain of hyperglycemic mice decreases synaptic inhibition of parasympathetic motor neurons in the dorsal motor nucleus of the vagus (DMV) and reduces systemic glucose levels. METHODS: Chemogenetic activation or inactivation of GABAergic neurons in the nucleus tractus solitarius (NTS) was used to assess effects of modulating parasympathetic output on blood glucose concentration in normoglycemic and hyperglycemic mice. Patch-clamp electrophysiology in vitro was used to assess cellular effects of chemogenetic manipulation of NTS GABA neurons. RESULTS: Chemogenetic activation of GABAergic NTS neurons in normoglycemic mice increased their action potential firing, resulting in increased inhibitory synaptic input to DMV motor neurons and elevated blood glucose concentration. Deactivation of GABAergic DVC neurons in normoglycemic mice altered their electrical activity but did not alter systemic glucose levels. Conversely, stimulation of GABAergic DVC neurons in mice that were hyperglycemic subsequent to treatment with streptozotocin changed their electrical activity but did not alter whole-body glucose concentration, while deactivation of this inhibitory circuit significantly decreased circulating glucose concentration. Peripheral administration of a brain impermeant muscarinic acetylcholine receptor antagonist abolished these effects. CONCLUSION: Disinhibiting vagal motor neurons decreases hyperglycemia in a mouse model of type 1 diabetes. This inhibitory brainstem circuit emerges as a key parasympathetic regulator of whole-body glucose homeostasis that undergoes functional plasticity in hyperglycemic conditions.

Adult Born Dentate Granule Cell Mediated Upregulation of Feedback Inhibition in a Mouse Model of Traumatic Brain Injury.

Post-traumatic epilepsy (PTE) and behavioral comorbidities frequently develop after traumatic brain injury (TBI). Aberrant neurogenesis of dentate granule cells (DGCs) after TBI may contribute to the synaptic reorganization that occurs in PTE, but how neurogenesis at different times relative to the injury contributes to feedback inhibition and recurrent excitation in the dentate gyrus is unknown. Thus, we examined whether DGCs born at different postnatal ages differentially participate in feedback inhibition and recurrent excitation in the dentate gyrus using the controlled cortical impact (CCI) model of TBI. Both sexes of transgenic mice expressing channelrhodopsin2 (ChR2) in postnatally born DGCs were used for optogenetic activation of three DGC cohorts: postnatally early born DGCs, or those born just before or after CCI. We performed whole-cell patch-clamp recordings from ChR2-negative, mature DGCs and parvalbumin-expressing basket cells (PVBCs) in hippocampal slices to determine whether optogenetic activation of postnatally born DGCs increases feedback inhibition and/or recurrent excitation in mice 8-10 weeks after CCI and whether PVBCs are targets of ChR2-positive DGCs. In the dentate gyrus ipsilateral to CCI, activation of ChR2-expressing DGCs born before CCI produced increased feedback inhibition in ChR2-negative DGCs and increased excitation in PVBCs compared with those from sham controls. This upregulated feedback inhibition was less prominent in DGCs born early in life or after CCI. Surprisingly, ChR2-positive DGC activation rarely evoked recurrent excitation in mature DGCs from any cohort. These results support that DGC birth date-related increased feedback inhibition in of DGCs may contribute to altered excitability after TBI.SIGNIFICANCE STATEMENT Dentate granule cells (DGCs) control excitability of the dentate gyrus through synaptic interactions with inhibitory GABAergic interneurons. Persistent changes in DGC synaptic connectivity develop after traumatic brain injury, contributing to hyperexcitability in post-traumatic epilepsy (PTE). However, the impact of DGC neurogenesis on synaptic reorganization, especially on inhibitory circuits, after brain injury is not adequately described. Here, upregulation of feedback inhibition in mature DGCs from male and female mice was associated with increased excitation of parvalbumin-expressing basket cells by postnatally born DGCs, providing novel insights into underlying mechanisms of altered excitability after brain injury. A better understanding of these inhibitory circuit changes can help formulate hypotheses for development of novel, evidence-based treatments for post-traumatic epilepsy by targeting birth date-specific subsets of DGCs.

Importance of macroprolactinemia in hyperprolactinemia.

Macroprolactin is an antigen-antibody complex of higher molecular mass than prolactin (>150kDa), consisting of monomeric prolactin and immunoglobulin G. The term 'macroprolactinemia' is used when the concentration of macroprolactin exceeds 60% of the total serum prolactin concentration determined by polyethylene glycol precipitation. The gold standard technique for the diagnosis of macroprolactinemia is gel filtration chromatography. The prevalence of macroprolactinemia in hyperprolactinemic populations varies between 15% and 35%. Although the pathogenesis of these antibodies is not clear, it is possible that changes in the pituitary prolactin molecule represent increased antigenicity to the immune system, leading to the production of anti-prolactin antibodies. Mild hyperprolactinemia usually occurs because macroprolactin is not cleared readily from the circulation due to its higher molecular weight. Moreover, the hypothalamic negative feedback mechanism for autoantibody-bound prolactin is inactive because macroprolactin cannot access the hypothalamus, resulting in hyperprolactinemia. Reduced in-vivo bioactivity of macroprolactin may be the reason for the lack of hyperprolactinemic symptoms. It also seems that anti-prolactin autoantibodies may compete with prolactin molecules for receptor binding, resulting in low bioactivity. Additionally, the large molecular size of macroprolactin confined in the intravascular compartment prevents its passage through the capillary endothelium to the target cells, which may be the reason for the lack of symptoms. Macroprolactinemia is considered to be a benign clinical condition in patients with normal concentrations of bioactive monomeric prolactin, with a lack, or low incidence, of hyperprolactinemic symptoms and negative pituitary imaging. In such cases with resistance to anti-prolactinaemic drugs, no pharmacological treatment, diagnostic investigations or prolonged follow-up are required. However, macroprolactinemia may also occur in patients with conventional symptoms of hyperprolactinemia who cannot be differentiated from patients with true hyperprolactinemia. These symptoms are mainly attributed to excess levels of monomeric prolactin, and this is of concern. The diagnosis of macroprolactinemia is misleading and inappropriate. A multitude of physiological, pharmacological and pathological causes, including stress, prolactinomas, hypothyroidism, renal and hepatic failure, intercostal nerve stimulation and polycystic ovary disease, can contribute to increased levels of monomeric prolactin. It is important for patients with elevated monomeric prolactin levels to undergo routine evaluation to identify the exact pathological state and introduce adequate treatment, regardless of the presence of macroprolactin. In addition, macroprolactinemia occasionally occurs due to macroprolactin associated with pituitary adenomas, with biological activity of macroprolactin comparable with that of monomeric prolactin. In cases when excess macroprolactin occurs with clinical manifestations of hyperprolactinemia, macroprolactinemia should be regarded as a pathological biochemical variant of hyperprolactinemia. An individualized approach to the management of such patients with macroprolactinemia may be necessary, and pituitary imaging, dopamine treatment and prolonged follow-up should be applied.

[Pseudotumoral tuberculosis of the cervix]. / Tuberculose pseudo-tumorale du col de l'utérus.

Cervical tuberculosis is a rare pathology, which can clinically look like a cervix cancer. The biopsy re-establishes the right diagnosis. The treatment is medical. The prognosis is primarily the infertility due to frequent associated general genital tuberculosis.

Mammographic pattern due to residual Lipiodol after galactography.

The purpose of this pictorial essay is to describe the different mammographic aspects of residual Lipiodol ultra fluid (LUF) after galactography, and to define some specific patterns, because it may in some cases mimic microcalcifications and give diagnostic problems. The mammograms of 14 patients, aged 32-63 years, presenting LUF residues related to previous galactography, were analyzed retrospectively. In 12 cases the diagnosis was easy because the patients presented a typical pattern on mammography and came with their initial galactography. In 2 cases the diagnosis was more difficult because the patients did not remember the previous injection and the progressive resorption mimicked perfectly intraductal calcification. Benign duct ectasia with inflammatory reaction to foreign bodies were found in 3 cases in which surgery was performed. Lipiodol ultra fluid is no longer used for galactography, but it may persist in breast ducts or cysts for years and seems to still be used in some countries. There are in most cases specific signs enabling the diagnosis.

Polyhedral microcalcifications on mammograms: prevalence and morphometric analysis.

OBJECTIVE: The purpose of this study was to determine the incidence and the mammographic appearance of polyhedral microcalcifications. MATERIALS AND METHODS: Prospectively, we evaluated screening mammograms in 2000 women for polyhedral microcalcifications. The number of polyhedral microcalcifications on routine and magnification views was established, and a quantitative analysis was done to determine if the shape of the polyhedral microcalcifications varied in the different projections. The ratio between the longer axis (R) and the shorter axis (r) was calculated. RESULTS: Two radiologists detected at least two polyhedral microcalcifications on one projection in 58 (3%) women. The number of polyhedral microcalcifications detected ranged from 2 to 47 (mean, 8.2) for screening mammograms and from 2 to 62 (mean, 13.4) on magnification views. Polyhedral microcalcifications were bilateral in 22 cases, scattered in one breast in 19 cases, segmental in 10 cases, and grouped in a cluster in seven cases. Lateral projections showed more rhombohedral microcalcifications, and craniocaudal projections showed more square microcalcifications. CONCLUSION: The frequency of polyhedral microcalcifications is 3%. The shape of polyhedral microcalcifications varies: craniocaudal views show them to be square and lateral views show them to be rhombohedral.

Nonsurgical therapy for stress incontinence.

This article discusses the therapies that have been developed for the treatment of stress incontinence due to female pelvic-floor dysfunction. A combination of pelvic muscle exercises, biofeedback, behavioral modification, and electrical stimulation are all treatment options that do not involve surgery. When physiotherapy proves successful, and surgery is avoided, it is necessary for the patient to be put on a maintenance program to avoid relapse. The authors also discuss the link between urinary stress incontinence and women involved in sports.