Morphologic evidence for intranuclear circuits in the hypothalamic arcuate nucleus

Three weeks after complete deafferentation of the medial basal hypothalamus (MBH) of adult female rats, the hypothalamic arcuate nucleus (ARCN) was examined ultrastructurally. Axodendritic and axosomatic synapses were counted in a field of 18,000 μm² in the middle part of the ARCN in each brain. Intraventricular infusion of 5-hydroxydopamine before autopsy resulted in the differentiation of two types of axon terminals. One axon terminal contained small spherical vesicles (SSVs, about 50 nm in diameter) and the other contained 5-hydroxydopamine-labeled small granular vesicles (SGVs) which were regarded as monoaminergic terminals. In the completely deafferented MBH, mean numbers of SSV and SGV synapses of the ARCN decreased to about one-half and one-fourth, respectively, compared to those of the unoperated rats. However, considerable numbers of intact SSV and SGV synapses were still encountered in the ARCN following deafferentation. There was no significant difference in the number of synapses between the large MBH island (including ARCN and ventromedial nucleus) and the small MBH island (mostly localized in ARCN). These results suggested that numerous converging nonmonoaminergic and monoaminergic fibers terminated in the ARCN and also suggested that nonmonoaminergic and monoaminergic arcuate neurons connected directly with other arcuate neurons.     

A new comprehensive ultrasonic diagnostic method for celiac artery compression syndrome that hybridizes “arterial compression hook sign” and peak systolic velocity

PurposeDiagnosing celiac artery compression syndrome (CACS) is based on an imaging finding of celiac artery compression (CAC), but the diagnostic criteria are inconsistent. The study aim was to devise an ultrasonographic screening method to effectively diagnose CAC in occult CACS.MethodsThe subjects were 61 patients with suspected CACS who underwent ultrasonography at our hospital from May 2017 to December 2019 and were divided into the following two groups: the “arterial compression hook sign”-positive group (n = 15, mean age: 26.6 ± 16.4 years, six males, nine females) and -negative group (n = 41, mean age: 32.5 ± 18.6 years, 12 males, 34 females). We used B-mode and advanced dynamic flow to detect arterial compression hook sign and pulse Doppler to measure expiration peak systolic velocity (EPSV) and inspiration PSV (IPSV).ResultsThe EPSV was significantly higher in the arterial compression hook sign-positive group (304.7 ± 47.4 cm/s) than in the -negative groups (158.2 ± 38.7 cm/s), (p < 0.001). Receiver operating characteristic curve analysis was performed to calculate the EPSV cutoff value for presence of CAC, which was 226 cm/s (sensitivity: 0.957, specificity: 1.000, AUC: 0.997, 95% confidence interval: 0.99–1). The IPSV was lower in the positive group than in the negative group in all cases (EPSV − IPSV range: 68–199 cm/s).ConclusionOur results showed that if arterial compression hook sign determined by B-mode ultrasound, EPSV > 226 cm/s, and IPSV decreases by ≥ 68 cm/s, then CAC can be detected with high specificity.Graphic abstract      

Arcuate foramen: prevalence by age,gender, and degree of calcification

The aim of the present study was to evaluate the prevalence of calcification of the oblique atlanto‐occipital ligaments (OAOLs, arcuate ligaments) relative to gender, age, and degree of calcification. Lateral cephalometric radiographs of 255 subjects presenting for orthodontic evaluation were reviewed. Population size was determined by power analysis. Two calibrated raters reviewed the films and classified the degree of calcification using a standardized rating scale. Class 1 ligaments demonstrated no calcification, Class 2 ligaments were less than half calcified, Class 3 ligaments were at least half calcified, and Class 4 ligaments were completely calcified. Of the subjects, 158 were Class 1 (62%), 70 were Class 2 (20%), 18 were Class 3 (7%), and 29 were Class 4 (11%). There was no evidence that the degree of ligamentous calcification of the arcuate ligaments differed by gender (p>0.10) or age (p=0.8891). This suggests that the anomaly is congenital in origin.     

Diurnal Rhythm in Proopiomelanocortin mRNA in the Arcuate Nucleus of the Male Rat

We tested the hypotheses that in the male rat, expression of proopiomelanocortin (POMC) mRNA in cells of the arcuate nucleus displays a diurnal fluctuation and that expression of this rhythm is dependent upon the secretory products of the testis. To accomplish this, we sacrificed groups of testes-intact and castrated adult male rats throughout the day and compared levels of POMC mRNA in individual cells of the arcuate nucleus across time and between groups. Adult male rats were housed on a 12–12 L D cycle with lights on a 0600 h and were divided into groups that were either castrated or left intact. Four days later, pairs from these groups were sacrificed at 0600 h, 1200 h, 1800 h, 2400 h, and again at 0600 h (n = 4 per group at each time point). We used in situ hybridization and a computerized image analysis system to measure cellular levels of POMC mRNA, as reflected by the number of autoradiographic grains over individual cells in the rostral quarter of the arcuate nucleus (counting ～ 30 cells per animal). Using cosinor analysis, we observed that in intact male rats, POMC mRNA levels varied significantly over the 24 h day with a nadir value at 1800 h. In contrast, there was no significant diurnal variation in POMC mRNA levels in castrated animals. POMC mRNA levels were significantly greater in the intact compared with castrated animals at every time point (P<0.01), except at 1800 h, when the groups did not differ significantly from one another. We conclude that adult male rats display at diurnal rhythm in cellular POMC mRNA levels in the arcuate nucleus, and we infer that testosterone or some other secretory product of the testis is a prerequisite for expression of this rhythm.     

老年大鼠弓状核内生长抑素mRNA的表达

采用原位杂交组织化学技术观察了老年大鼠弓状核内生长抑素信使核糖核酸的表达。和年青大鼠相比，老年大鼠弓核内生长抑素ｍＲＮＡ阳性胞体大多染色浅淡，与背景反差小，数量上明显减少。结果提示：在衰老过程中，弓状核内生长抑素减少可能对机体内分泌和神经内分泌功能的进行性衰退有重要作用。     

Hypoactive Sexual Desire Disorder: International Society for the Study of Women's Sexual Health (ISSWSH) Expert Consensus Panel Review

The objective of the International Society for the Study of Women's Sexual Health expert consensus panel was to develop a concise, clinically relevant, evidence-based review of the epidemiology, physiology, pathogenesis, diagnosis, and treatment of hypoactive sexual desire disorder (HSDD), a sexual dysfunction affecting approximately 10% of adult women. Etiologic factors include conditions or drugs that decrease brain dopamine, melanocortin, oxytocin, and norepinephrine levels and augment brain serotonin, endocannabinoid, prolactin, and opioid levels. Symptoms include lack or loss of motivation to participate in sexual activity due to absent or decreased spontaneous desire, sexual desire in response to erotic cues or stimulation, or ability to maintain desire or interest through sexual activity for at least 6 months, with accompanying distress. Treatment follows a biopsychosocial model and is guided by history and assessment of symptoms. Sex therapy has been the standard treatment, although there is a paucity of studies assessing efficacy, except for mindfulness-based cognitive behavior therapy. Bupropion and buspirone may be considered off-label treatments for HSDD, despite limited safety and efficacy data. Menopausal women with HSDD may benefit from off-label testosterone treatment, as evidenced by multiple clinical trials reporting some efficacy and short-term safety. Currently, flibanserin is the only Food and Drug Administration–approved medication to treat premenopausal women with generalized acquired HSDD. Based on existing data, we hypothesize that all these therapies alter central inhibitory and excitatory pathways. In conclusion, HSDD significantly affects quality of life in women and can effectively be managed by health care providers with appropriate assessments and individualized treatments.     

Growth hormone secretagogues and hypothalamic networks

Growth hormone secretagogues (GHSs) act at distinct levels to control growth hormone (GH) secretion. At the pituitary level they reinforce or extend a tonic GH-releasing-hormone (GHRH)-induced activated state by mobilizing intracellular Ca²⁺ store. At the hypothalamic level GHS actions are more complex than originally anticipated. Chronic treatments with GHS result in loss of responsiveness to the secretagogues, an effect probably accounted for by indirect negative feedback of GHS stimulated plasma GH levels over GHRH release. Moreover, intracerebroven-tricular treatments with GHS can have paradoxical, inhibitory effects on GH secretion. Several mechanisms can account for such dual effects. GHS receptors were found to extend far beyond the arcuate nucleus and are mainly coexpressed, by GHRH, somatostatin, and neuropeptide Y (NPY) neurons. Activation of GHRH neurons by GHS can be direct or indirect. Indeed using antisense strategy we found that sst1 are physiological activators of arcuate GHRH neurons and we propose that activation of SRIH arcuate interneurons by GHS can increase GHRH neuron activity. Moreover, GHS can stimulate distinct populations of NPY neurons having opposite effects on GH secretion: arcuate NPY interneurons, act as indirect facilitators of GHRH release, whereas, on the contrary, a different subset of NPY neurons projecting to the periventricular hypothalamus (those also involved in mediating leptin effects on GH) seems able to activate SRIH release.     

Renal Arcuate Vein Microthrombi-Associated AKI

Backgrounds and objectives

This report describes six patients with AKI stages 2–3 (median admission creatinine level, 2.75 mg/dl [range, 1.58–5.44 mg/dl]), hematuria (five with hemoproteinuria), and unremarkable imaging with an unusual and unexplained histologic diagnosis on renal biopsy.

Design, setting, participants, & measurements

The patients were young adults who presented to two neighboring United Kingdom nephrology centers over a 40-month period (between July 2010 and November 2013). Four were male, and the median age was 22.5 years (range, 18–27 years). Their principal symptoms were flank pain or lower back pain. All had consumed alcohol in the days leading up to admission.

Results

Renal biopsy demonstrated microthrombi in the renal arcuate veins with a corresponding stereotypical, localized inflammatory infiltrate at the corticomedullary junction. All patients recovered to baseline renal function with supportive care (median, 17 days; range, 6–60 days), and none required RRT. To date, additional investigations have not revealed an underlying cause for these histopathologic changes. Investigations have included screening for thrombophilic tendencies, renal vein Doppler ultrasonographic studies, and testing for recreational drugs and alcohol (including liquid chromatography–mass spectrometry of urine) to look for so-called designer drugs. Inquiries to the United Kingdom National Poisons Information Centre have identified no other cases with similar presentation or histologic findings.

Conclusions

Increased awareness and additional study of future cases may lead to a greater understanding of the underlying pathophysiologic mechanisms that caused AKI in these patients.     

Detection of mesenteric ischemia by means of endoscopic visible light spectroscopy after luminal feeding

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