Unraveling the Membrane Topology of TMEM151A: A Step Towards Understanding its Cellular Role.

Transmembrane protein 151A (TMEM151A) has been identified as a causative gene for paroxysmal kinesigenic dyskinesia, though its molecular function remains almost completely unknown. Understanding the membrane topology of transmembrane proteins is crucial for elucidating their functions and possible interacting partners. In this study, we utilized molecular dynamics simulations, immunocytochemistry, and electron microscopy to define the topology of TMEM151A.

Case Report: Novel biallelic moderately damaging variants in in a patient with cerebellar dysplasia.

Rotatin, encoded by the gene, is a centrosomal protein with multiple, emerging functions, including left-right specification, ciliogenesis, and neuronal migration. Recessive variants in are associated with a neurodevelopmental disorder with microcephaly and malformations of cortical development known as "Microcephaly, short stature, and polymicrogyria with seizures" (MSSP, MIM #614833). Affected individuals show a wide spectrum of clinical manifestations like intellectual disability, poor/absent speech, short stature, microcephaly, and congenital malformations.

Missense mutations in the membrane domain of PRRT2 affect its interaction with Nav1.2 voltage-gated sodium channels.

PRRT2 is a neuronal protein that controls neuronal excitability and network stability by modulating voltage-gated Na channel (Nav). PRRT2 pathogenic variants cause pleiotropic syndromes including epilepsy, paroxysmal kinesigenic dyskinesia and episodic ataxia attributable to loss-of-function pathogenetic mechanism. Based on the evidence that the transmembrane domain of PRRT2 interacts with Nav1.

The intramembrane COOH-terminal domain of PRRT2 regulates voltage-dependent Na channels.

Proline-rich transmembrane protein 2 (PRRT2) is the single causative gene for pleiotropic paroxysmal syndromes, including epilepsy, kinesigenic dyskinesia, episodic ataxia, and migraine. PRRT2 is a neuron-specific type-2 membrane protein with a COOH-terminal intramembrane domain and a long proline-rich NH-terminal cytoplasmic region. A large array of experimental data indicates that PRRT2 is a neuron stability gene that negatively controls intrinsic excitability by regulating surface membrane localization and biophysical properties of voltage-dependent Na channels Nav1.

Hemodialysis tunneled central venous catheters: five-year outcome analysis.

Background: Tunneled central venous catheters (tCVCs) are considered inferior to arteriovenous fistulas (AVFs) and grafts in all nephrology guidelines. However, they are being increasingly used as hemodialysis vascular access. The purpose of this study was to document the natural history of tCVCs and determine the rate and type of catheter replacement.

Renal antifibrotic effect of N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.

Background And Aim: Diabetic nephropathy is the main cause of end-stage renal disease. N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP), a physiological tetrapeptide hydrolyzed by the angiotensin-converting enzyme (ACE), has antifibrotic effects in the cardiovascular system and in the kidney in experimental models of hypertension, heart failure and renal disease. The aim of the study was to evaluate the effect of Ac-SDKP in diabetic nephropathy and the potential additive effect of Ac-SDKP, when compared to ACE inhibitors alone, on the development of renal fibrosis.

Evaluation of the impact of a new synthetic vitamin E-bonded membrane on anemia and rHuEPO requirement in ESRD patients with central venous catheters: a pilot study.

In the last years, the number of hemodialysis (HD) patients with erythropoietin (rHuEPO) resistance is increasing. Probably, central venous catheters (CVCs) contribute to this resistance by inducing inflammation and oxidative stress. This study was aimed to compare vitamin E-bonded dialyzer (PSVE) versus polyethersulfone membrane.

MiR-133a regulates collagen 1A1: potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension.

MicroRNAs play an important role in myocardial diseases. MiR-133a regulates cardiac hypertrophy, while miR-29b is involved in cardiac fibrosis. The aim of this study was to evaluate whether miR-133a and miR-29b play a role in myocardial fibrosis caused by Angiotensin II (Ang II)-dependent hypertension.

Prevention of myocardial fibrosis by N-acetyl-seryl-aspartyl-lysyl-proline in diabetic rats.

Ac-SDKP (N-acetyl-seryl-aspartyl-lysyl-proline) is a physiological tetrapeptide hydrolysed by ACE (angiotensin-converting enzyme). In experimental models of hypertension, Ac-SDKP has antifibrotic effects in the heart; however, the role of Ac-SDKP in diabetic cardiomyopathy is currently unknown. The aim of the present study was to evaluate the effect of Ac-SDKP on cardiac systolic and diastolic function, and interstitial and perivascular fibrosis in the heart of diabetic rats.

Efficient detection of leukemia-related fusion transcripts by multiplex PCR applied on a microelectronic platform.

The identification of prognostically relevant fusion genes is required in the routine diagnostic process of most advanced clinical protocols for leukemia patients, either for risk stratification, target-specific treatments, and/or as markers for monitoring Minimal Residual Disease during treatment. However, there is emerging need to implement diagnostics and patient classification based on other biological features, such as expression levels of specific genes or genomic polymorphisms and/or mutations. This advancement would ideally be pursued in a diagnostic laboratory by an unique platform capable of different diagnostic purposes.

[Acute renal failure and thrombotic microangiopathy (TM)].

Background: Thrombotic microangiopathy (TM) is a disorder characterized by fibrin formation and platelet aggregation in the small arteries and capillaries. Two main clinical settings are reported in association with this disorder: hemolitic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). Both conditions share common findings such as microangiopathic anemia and thrombocytopenia.

Family-based association study of 5-HTTLPR, TPH, MAO-A, and DRD4 polymorphisms in mood disorders.

Variants of the functional polymorphism in the serotonin transporter (upstream regulatory region: 5-HTTLPR), the tryptophan hydroxylase (TPH), the monoamine oxidase A (MAO-A), and the dopamine receptor D4 (DRD4) genes have all been associated with mood disorders. The aim of this study was to test those hypotheses by using a family-based association approach. Both diagnoses and psychopathology were used for phenotype definitions.

Long-term effects of intravenous calcitriol therapy on the control of secondary hyperparathyroidism.

Although high-dose intravenous calcitriol has been shown to be effective in suppressing parathyroid hormone (PTH) secretion in dialysis patients with secondary hyperparathyroidism, an increasing number of patients is refractory to treatment. Only a few studies have evaluated the factors that can predict a favorable response to calcitriol, but contrasting results have been reported. This study was performed to evaluate the effect of high-dose intravenous calcitriol on parathyroid function and to investigate the factors that can predict a favorable response to treatment.

Protein nitrogen appearance in CAPD patients: what is the best formula?

Background: The protein equivalent of nitrogen appearance is an indirect index commonly used to assess dietary protein intake in patients on CAPD. Moreover it has been suggested that the ratio between nitrogen appearance and dietary nitrogen intake (fractional urea synthesis) can predict nitrogen balance in uraemic patients. Several formulae to directly calculate the protein equivalent of nitrogen appearance have been published.

Effect of CAPD and hemodialysis on parathyroid function.

Unlabelled: A high incidence of low turnover bone disease (LTBD) has been reported in predialysis and dialysis uremic patients, despite parathyroid hormone (PTH) levels two- to four-fold the upper normal limit. The aim of this study was to evaluate the trend of PTH in uremic patients after admission to continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD). Thus, we evaluated 53 patients (27 CAPD and 26 HD) of 73 consecutive uremic patients starting CAPD or HD from 1992, who had at least one year follow-up on dialysis.

Different effects of calcitriol and parathyroidectomy on the PTH-calcium curve in dialysis patients with severe hyperparathyroidism.

Background: The PTH-calcium sigmoidal curve is shifted to the right, the slope of the curve is steeper, and the set point of calcium is increased in dialysis patients with secondary hyperparathyroidism, compared to patients with low-turnover bone disease. These findings could be related to increased parathyroid cell mass and increased sensitivity of parathyroid cells to serum calcium variations in these patients. Calcitriol therapy has been documented to reduce PTH levels by shifting the curve to the left and downward.

High-dose oral calcitriol and zero calcium peritoneal solutions in CAPD patients with refractory secondary hyperparathyroidism.

We evaluated the effect of pulse oral calcitriol (4 micrograms three times weekly for 6 months) on parathyroid function in nine CAPD patients with hyperparathyroidism refractory to conventional low-dose oral calcitriol. Zero calcium peritoneal solutions were used to prevent the development of hypercalcaemia. The peritoneal loss of calcium increased from 168 +/- 40 to 417 +/- 48 mg/day using zero calcium solutions.

Calcium balance and serum ionized calcium fluctuations in on-line haemodiafiltration in relation to ultrafiltration rate and dialysate calcium concentration.

The use of high ultrafiltration rates in haemodiafiltration (HDF) has been suggested for improving the clearance of small and large molecules. This strategy has become economically applicable with the development of safe techniques for on-line production of sterile infusate from dialysate, which enables us to infuse large substitution fluid volumes without further increasing the cost of sessions. The effect of increasing the ultrafiltration rate in HDF on electrolyte balance has not yet been evaluated.

The sigmoidal parathyroid hormone-ionized calcium curve and the set point of calcium in hemodialysis and continuous ambulatory peritoneal dialysis.

A high incidence of adynamic bone disease not related to aluminum intoxication has been reported in continuous ambulatory peritoneal dialysis (CAPD). Since reduced parathyroid hormone (PTH) secretion may predispose to adynamic bone, we investigated whether parathyroid gland sensitivity may be depressed in CAPD in comparison with hemodialysis (HD). Thus we determined parathyroid function by the evaluation of the PTH-ionized calcium (ICa) relationship, which was obtained inducing hypocalcemia and hypercalcemia in 19 CAPD and 18 HD patients with biochemical and histological evidence of mild (MILD) or severe (OF) hyperparathyroidism, but negative stainable bone aluminum.

Computerized management of peritoneal dialysis.

The importance of the evaluation of dialytic adequacy is well known in peritoneal dialysis. It is necessary to be able to quantify and individualize the substitution treatment. In 15 patients we compared five quantitative approaches by using original software: Teehan's dialysis index (DI); Diaz-Buxo's liters/week (LW); Keshaviah's the quantity of dialysis prescribed (wKt/V); and Boen and Twardowski's weekly creatinine clearance (WC).

Calcium mass transfer and kinetics in CAPD using calcium-free solutions.

In 12 continuous ambulatory peritoneal dialysis (CAPD) patients we evaluated peritoneal calcium mass transfer (CaMT), serum and effluent dialysate ionized calcium (iCa) changes, and the variations of the dialysate-to-plasma (D/P) ratio for calcium throughout 6-hour dwell exchanges with zero calcium, 1.25 mmol/L calcium (1.25 Ca), and 1.

Adequacy of haemodiafiltration.

In this study we have evaluated the influence of blood and ultrafiltration flow rate on the performance of five different high-flux membrane dialysers during haemodiafiltration. On the basis of clearance data we optimised the haemodiafiltration schedule of six uraemic patients to maintain an adequate midweek blood urea nitrogen concentration, while reducing the treatment time from 285 +/- 23 min to 210 min. After a follow-up of 6 months, we observed no difference in the clinical tolerance or in the biochemical parameters, compared to those found during the preceding haemodialysis period.