Growth hormone resistance in uremia

Growth retardation is a major complication in children with uremia. Protein restriction, calorie deficit, metabolic acidosis, renal osteodystrophy, and endocrinologic disturbances contribute to the growth failure. The effect of these factors on growth retardation can be attenuated in part by therapy with vitamin D metabolites, adequate nutrition, alkalization, and dialysis. Linear growth in children with uremia is markedly retarded despite normal or increased levels of circulating serum growth hormone. An increased growth hormone level in children with uremia is due to normal growth hormone secretion from the pituitary gland and impaired growth hormone clearance in the kidney. However, the elevated growth hormone level does not lead to a commensurate rise in serum insulin-like growth factor I (IGF-I); the serum IGF-I level is decreased or normal in relation to the degree of renal failure. This discrepancy suggests growth hormone resistance in the liver in uremia. Recent molecular techniques open a new era in studying the gene expression for growth hormone or IGF-I. There is no doubt today that growth hormone treatment has the beneficial effect of growth promotion in children with uremia, which also suggests endogenous growth hormone resistance in target organs or target cells in uremia.     

High-dose methylprednisolone therapy for nephrotic syndrome in Henoch-Schoenlein nephritis

Twelve patients with nephrotic syndrome (NS) in Henoch-Schoenlein (HS) nephritis were treated with a high dose of intravenous methylprednisolone (MP) on each of nine alternate days followed by oral prednisolone for 4 to 6 months. Renal biopsy was performed on 10 of the 12 patients. The glomerular change in 5 patients, which was accompanied by crescents and/or sclerosis, with NS and acute nephritic syndrome (ANS) at onset, was more severe than that of the other 5 patients with NS and hematuria at onset. The renal insufficiency or hypertension in these 5 patients with NS and ANS improved within 2 weeks on this MP therapy. After a mean follow-up period of 40.5 months, all patients except 2 revealed normal physical findings and renal function as well as urinary findings. Repeated biopsies in the 2 patients with NS and ANS at onset demonstrated an improved renal pathology in comparison with their initial biopsies. No severe side effects related to high-dose intravenous MP followed by oral prednisolone therapy were encountered in any of the patients. Our results suggest that high-dose intravenous MP therapy can lead to a favorable outcome in patients with NS in HS nephritis.     

Camostat mesilate attenuates pancreatic fibrosis via inhibition of monocytes and pancreatic stellate cells activity

Camostat mesilate (CM), an oral protease inhibitor, has been used clinically for the treatment of chronic pancreatitis in Japan. However, the mechanism by which it operates has not been fully understood. Our aim was to evaluate the therapeutic efficacy of CM in the experimental pancreatic fibrosis model induced by dibutyltin dichloride (DBTC), and we also determined the effect of CM on isolated monocytes and panceatic stellate cells (PSCs). In vivo, chronic pancreatitis was induced in male Lewis rats by single administration of 7 mg/kg DBTC and a special diet containing 1 mg/g CM was fed to the DBTC+CM-treated group from day 7, while the DBTC-treated group rats were fed a standard diet. At days 0, 7, 14 and 28, the severity of pancreatitis and fibrosis was examined histologically and enzymologically in both groups. In vitro, monocytes were isolated from the spleen of a Lewis rat, and activated with lipopolysaccharide stimulation. Thereafter, the effect of CM on monocyte chemoattractant protein-1 (MCP-1) and tumor necrosis factor-alpha (TNF-alpha) production from monocytes was examined. Subsequently, cultured rat PSCs were exposed to CM and tested to see whether their proliferation, MCP-1 production and procollagen alpha1 messenger RNA expression was influenced by CM. In vivo, the oral administration of CM inhibited inflammation, cytokines expression and fibrosis in the pancreas. The in vitro study revealed that CM inhibited both MCP-1 and TNF-alpha production from monocytes, and proliferation and MCP-1 production from PSCs. However, procollagen alpha1 expression in PSCs was not influenced by CM. These results suggest that CM attenuated DBTC-induced rat pancreatic fibrosis via inhibition of monocytes and PSCs activity.     

Immunoelectron microscopic observations of hypothalamic TRH-containing neurons in rats

Summary Immunoreactive TRH-containing neurons and their synaptic associations were studied electron microscopically in the paraventricular nucleus (PVN) and dorsomedial nucleus (DMH) of the rat hypothalamus. In propylthiouracil (PTU)-treated rats, the immunoreactive cell bodies in the PVN appeared to be activated, showing a hypertrophic perikaryon, well developed Golgi bodies and numerous secretory granules. No such alterations were evident in the TRH neurons in the DMH. These findings suggest that the PVN-TRH neurons are involved in the hypothalamic-hypophysial-thyroid axis. Further, it was shown that unlabeled nerve terminals containing small and large clear vesicles make synaptic contacts with the TRH perikarya in the PVN. Thus it is likely that PVN-TRH neurons are regulated both by thyroid hormones and by other neuronal signals. In the DMH, unlabeled nerve terminals containing small and large clear vesicles, and immunoreactive terminals form synapses with TRH neurons. Thus the DMH-TRH neurons may be under dual neuronal control. It was further noted that in the DMH and PVN, TRH nerve terminals make synaptic contacts with other unlabeled neurons. It is evident that TRH acts as a neurotransmitter or neuromodulator, although the origin of TRH terminals should be elucidated.     

Suprachiasmatic nucleus neurons immunoreactive for vasoactive intestinal polypeptide have synaptic contacts with axons immunoreactive for neuropeptide Y: an immunoelectron microscopic study in the rat

An electron microscopic study showed by using a dual immunolabeling technique that in the suprachiasmatic nucleus of the rat, axon terminals immunoreactive for neuropeptide Y (NPY) made synaptic contacts upon neurons immunoreactive for vasoactive intestinal polypeptide (VIP). Diaminobenzidine (DAB)-labeled NPY axon terminals made synaptic contacts on silver-gold-labeled VIP perikarya and dendritic processes. The presynaptic NPY terminals contained many small clear vesicles and a few cored vesicles labeled with DAB chromogen. At the synaptic portion, a symmetrical thickening of the pre- and post-synaptic membranes was evident.     

Neurophysiological Testing to Assess Penile Sensory Nerve Damage After Radical Prostatectomy

IntroductionRadical prostatectomy (RP) can lead to erectile dysfunction due to surgical injury of the cavernous nerves. However, there is no simple, objective test to evaluate cavernous nerve damage caused by RP in clinical practice.AimTo assess the value of the measurement of penile thermal and vibratory sensory thresholds to reflect cavernous nerve damage caused by RP.MethodsWe included 42 consecutive patients who underwent RP with cavernous nerve sparing (laparoscopic approach, N = 12) or without cavernous nerve sparing (laparoscopic, N = 13; retropubic, N = 11; or transperineal, N = 6). Penile thermal (warm and cold) and vibratory sensory thresholds were measured twice, together with the Erectile Dysfunction Symptom Score (EDSS), 1 month before and 2 months after RP.Main Outcome MeasuresPenile sensory thresholds for warm, cold, and vibration sensations.ResultsPenile sensory thresholds for warm (P < 0.0001) and cold (P < 0.0001) sensations significantly increased after non‐nerve‐sparing RP, but not after nerve‐sparing RP. Vibration threshold only increased after transperineal non‐nerve‐sparing RP (P = 0.031). EDSS values were significantly increased in all groups of patients 2 months after surgery.ConclusionsSensory nerve fibers carrying penile skin sensations travel with the cavernous nerves in the pelvis. Therefore, testing these sensations may help to evaluate the extent of cavernous nerve damage caused by RP. In this series, post‐operative changes in penile sensory thresholds differed with the surgical technique of RP, as the cavernous nerves were preserved or not. The present results support the value of quantitative penile sensory threshold measurement to indicate RP‐induced cavernous nerve injury. Yiou R, De Laet K, Hisano M, Salomon L, Abbou C‐C, and Lefaucheur J‐P. Neurophysiological testing to assess penile sensory nerve damage after radical prostatectomy. J Sex Med 2012;9:2457–2466.     

Timing of Uterine Artery Embolization for Leiomyoma during the Menstrual Cycle

PurposeTo investigate differences in outcomes of uterine artery embolization (UAE) for leiomyoma when performed during different phases of the menstrual cycle.Materials and MethodsIn this single-institution retrospective analysis, 111 premenopausal patients (median [range] age, 44 [33–52] years) undergoing UAE for symptomatic leiomyoma between June 2014 and February 2020 were included. Twenty-one patients underwent UAE in the menstrual phase (the early follicular phase), 27 in the late follicular phase, and 63 in the luteal phase. Baseline characteristics and technical and peri-procedural outcomes were compared among groups. Leiomyoma infarction on contrast-enhanced magnetic resonance imaging 1 week after UAE and 4-month outcomes, including changes in the Uterine Fibroid Symptom and Quality of Life questionnaire scores, the volume reduction rates of the uterus and largest leiomyoma, follicle stimulating hormone values, adverse events, and amenorrhea, were compared among groups.ResultsA 4-month follow-up was completed for all patients. No significant differences were observed among groups in baseline characteristics or technical and peri-procedural outcomes. There were no significant differences in the multivariate-adjusted 1-week infarction rates of all leiomyoma volumes (P = .161) or multivariate-adjusted 4-month outcomes, including changes in the Uterine Fibroid Symptom and Quality of Life questionnaire symptoms and total scores (P = .864 and P = .798, respectively), the volume reduction rates of the uterus and the largest leiomyoma (P = .865 and P = .965, respectively), and follicle stimulating hormone values (P = .186) among the groups. No significant differences were noted in the 4-month adverse events (P = .260) or amenorrhea (P = .793) among the groups.ConclusionsThe present study demonstrated no significant differences in the outcomes of UAE for leiomyoma when performed during different phases of the menstrual cycle.     

Hypoproteinemia in the second trimester among patients with preeclampsia prior to the onset of clinical symptoms

Objective: To find a risk factor for “uncomplicated” preeclampsia (PE) comparing blood biochemical parameters between women with uncomplicated PE and healthy pregnant women in each trimester of pregnancy. Methods: A retrospective study was performed on 83 cases of uncomplicated PE, selected from 434 patients with PE, disregarding subjects with other complications relevant to hypertension during pregnancy. The study was limited to women with PE occurring in the third trimester, and records of blood biochemical parameters were evaluated. Controls were recruited from 108 healthy volunteers with normal singleton pregnancies. Results: A significant decrease in total protein was observed in the uncomplicated PE group in the second trimester prior to the onset of clinical symptoms. Conclusion: Hypoproteinemia during pregnancy may be a risk factor for this pathophysiology, and the maintenance of sufficient protein in early pregnancy could contribute to prophylaxis for women with uncomplicated PE.