Hemorheological follow-up after splenectomy and spleen autotransplantation in mice

We previously reported on a spleen autotransplantation model in mice, with spleen function studies at 6 weeks. The present study was undertaken to investigate long-term hemorheological functions. A/J and BALB/c inbred mice were divided into four groups: control, sham surgery (SH), splenectomy (SE), and spleen autotransplantation (AU). Hematological and hemorheological parameters were determined. Leukocyte counts in the SE and AU groups were significantly higher than in controls, while hematocrit levels were markedly lower. Mean erythrocyte volume did not change significantly. Platelet counts in the AU group were significantly lower, and red blood cell deformability was significantly worse in the SE group. The AU group also had increased cell transit time, but it was less than that in the SE group. The SE group showed the highest fibrinogen levels. We conclude that there are some consistent differences in hematological parameters between splenectomy and spleen autotransplantation. These data suggest that spleen autotransplantation may partially restore hemorheological functions following splenectomy.     

Role of estrogen receptor alpha on vaginal epithelialization of patients with Mayer–Rokitansky–Kuster–Hauser syndrome submitted to neovaginoplasty using oxidized regenerated cellulose

Introduction and hypothesis  

The purpose of this study was to evaluate the expression of estrogen receptor alpha (ERα) on the neovaginal tissue of patients with Mayer–Rokitansky–Kuster–Hauser (MRKH) syndrome submitted to modified Abbé-McIndoe neovaginoplasty using oxidized regenerated cellulose.     

Frequency‐dependent regulation of intrinsic excitability by voltage‐activated membrane conductances,computational modeling and dynamic clamp

As one of the most unique properties of nerve cells, their intrinsic excitability allows them to transform synaptic inputs into action potentials. This process reflects a complex interplay between the synaptic inputs and the voltage‐dependent membrane currents of the postsynaptic neuron. While neurons in natural conditions mostly fire under the action of intense synaptic bombardment and receive fluctuating patterns of excitation and inhibition, conventional techniques to characterize intrinsic excitability mainly utilize static means of stimulation. Recently, we have shown that voltage‐gated membrane currents regulate the firing responses under current step stimulation and under physiologically more realistic inputs in a differential manner. At the same time, a multitude of neuron types have been shown to exhibit some form of subthreshold resonance that potentially allows them to respond to synaptic inputs in a frequency‐selective manner. In this study, we performed virtual experiments in computational models of neurons to examine how specific voltage‐gated currents regulate their excitability under simulated frequency‐modulated synaptic inputs. The model simulations and subsequent dynamic clamp experiments on mouse hippocampal pyramidal neurons revealed that the impact of voltage‐gated currents in regulating the firing output is strongly frequency‐dependent and mostly affecting the synaptic integration at theta frequencies. Notably, robust frequency‐dependent regulation of intrinsic excitability was observed even when conventional analysis of membrane impedance suggested no such tendency. Consequently, plastic or homeostatic regulation of intrinsic membrane properties can tune the frequency selectivity of neuron populations in a way that is not readily expected from subthreshold impedance measurements.     

Social inequalities in response to antidepressant treatment in older adults

CONTEXT: We examined the relationship between socioeconomic status and response to treatment for depression among older adults. METHODS: Secondary analysis of pooled data from the open-label phase of 2 National Institute of Mental Health-funded clinical trials of nortriptyline hydrochloride or paroxetine combined with interpersonal psychotherapy (N = 248). We used Cox proportional hazards regression analyses to examine the association between socioeconomic status, indexed by census tract median annual household income and the subject's educational attainment, and treatment response and remission according to the Hamilton Depression Rating Scale. The association between socioeconomic status and suicidality or depressed mood reported at each week of treatment was examined using repeated-measures generalized logit models. RESULTS: Subjects residing in middle-income census tracts were significantly more likely to respond to antidepressant treatment than subjects residing in low-income census tracts (adjusted hazard ratio, 1.80; 95% confidence interval [CI], 1.18-2.75]). Throughout the course of antidepressant treatment, subjects in the middle- and high-income census tracts were significantly less likely to report suicidal ideation (adjusted odds ratios, 0.48 [95% CI, 0.27-0.94] and 0.39 [95% CI, 0.16-0.94], respectively). No association was found between socioeconomic status and remission. CONCLUSION: Residence in a low-income census tract is associated with a less favorable course of depression among older adults receiving a combination of pharmacologic and psychosocial treatment.     

Effectiveness of adding voluntary pelvic floor muscle contraction to a Pilates exercise program: an assessor-masked randomized controlled trial

Introduction and hypothesis

The purpose of this study was to evaluate the effectiveness of adding voluntary pelvic floor muscle contraction (PFMC) to a Pilates exercise program in sedentary nulliparous women.

Methods

Fifty-seven healthy nulliparous and physically inactive women were randomized to a Pilates exercise program (PEP) with or without PFMC. Forty-eight women concluded this study (24 participants for each group). Each woman was evaluated before and after the PEP, by a physiotherapist and an urogynecologist (UG). Neither of the professionals was revealed to them. This physiotherapist measured their pelvic floor muscle strength by using both a perineometer (Peritron) and vaginal palpation (Oxford Scale). The UG, who performed 3D perineal ultrasound examinations, collected their data and evaluated the results for pubovisceral muscle thickness and the levator hiatus area (LA). Both professionals were blinded to the group allocation. The protocol for both groups consisted of 24 bi-weekly 1-h individual sessions of Pilates exercises, developed by another physiotherapist who specializes in PFM rehabilitation and the Pilates technique.

Results

The PEP+ PFMC group showed significantly greater strength improvements than the PEP group when comparing the Oxford scale, vaginal pressure and pubovisceral muscle thickness during contraction measurements at baseline and post-treatment.

Conclusions

Our findings suggest that adding a voluntary PFMC to a Pilates exercise program is more effective than Pilates alone in improving PFM strength in sedentary nulliparous women.

     

Multidisciplinary education and lifestyle camps for CKD patients and their closest family members: effects on disease progression,self-management and psychosocial condition—a retrospective cohort study

Background

Multidisciplinary education including psychosocial care (MDE) may alleviate high burden of chronic kidney disease (CKD). Family support also has utmost importance, yet, MDE has rarely been provided jointly for patients and their relatives.

Methods

We organized intensive, 1-week-long boarding MDE and lifestyle camps for CKD stage III–V patients and their relatives and assessed the rate of CKD progression, proportion of participants’ home-based dialysis choice, transplant activity, and improvement of their coping and attitude evaluated by written narratives. Outcome was compared to 40 controls with similarly advanced CKD, under standard of care on our outpatient clinic.

Results

In 60 predialysis patients, serum creatinine 12 months before participation was 281 [IQR 122] µmol/l, right before MDE 356 [IQR 141] µmol/l, 12 months after MDE 388 [IQR 284] µmol/l, eGFR decreased from 18.5 [IQR 10] ml/min to 14.0 [IQR 7] ml/min and 13.0 [IQR 8] ml/min, respectively. Twelve months’ changes before and after MDE differed significantly (p?=?0.005 for creatinine; p?=?0.003 for eGFR). Decreased progression was found in comparison to controls (p?=?0.004; 0.016, respectively) as well. During follow-up, MDE patients compared to controls chose PD as dialysis modality more often (p?=?0.004), and were more active in renal transplantation (p?=?0.026). Based on narratives, MDE enhanced participants’ disease-specific knowledge and ability for coping. It also improved sympathy, helpfulness, and the mutual responsibilities of family members.

Conclusions

Our unique MDE programme with participation of the closest relatives enhanced the effectiveness of education and strengthened family support, which contributed to favorable CKD outcome, increased activity in home-based dialysis selection and transplant activity.

     

Biochemical and pharmacological characterization of 2-(9-(2-piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071), a novel,orally active elastase inhibitor

Human leukocyte elastase (HLE) is a proteinase capable of degrading a variety of proteins. Under normal circumstances, the proteolytic activity of HLE is effectively controlled by its natural inhibitors. However, an imbalance between elastase and its endogenous inhibitors may result in several pathophysiological states such as chronic obstructive pulmonary disease, asthma, emphysema, cystic fibrosis, and chronic inflammatory diseases. It is anticipated that an orally active HLE inhibitor could be useful for the treatment of these diseases. 2-(9-(2-Piperidinoethoxy)-4-oxo-4H-pyrido[1,2-a]pyrimidin-2-yloxymethyl)-4-(1-methylethyl)-6-methoxy-1,2-benzisothiazol-3(2H)-one-1,1-dioxide (SSR69071) is a potent inhibitor of HLE, with the inhibition constant (K(i)) and the constant for inactivation process (k(on)) being 0.0168 +/- 0.0014 nM and 0.183 +/- 0.013 10(6)/mol sr, respectively. The dissociation rate constant, k(off), was 3.11 + 0.37 10(-6)/s. SSR69071 displays a higher affinity for human elastase than for rat (K(i) = 3 nM), mouse (K(i) = 1.8 nM), and rabbit (K(i) = 58 nM) elastases. Bronchoalveolar lavage fluid from mice orally treated with SSR69071 inhibits HLE (ex vivo), and in this model, SSR69071 has a dose-dependent efficacy with an ED(50) = 10.5 mg/kg p.o. SSR69071 decreases significantly the acute lung hemorrhage induced by HLE (ED(50) = 2.8 mg/kg p.o.) in mice. Furthermore, SSR69071 prevents carrageenan- (ED(30) = 2.2 mg/kg) and HLE-induced (ED(30) = 2.7 mg/kg) paw edema in rats after p.o. administration. In conclusion, SSR69071 is a selective, orally active, and potent inhibitor of HLE with good penetration in respiratory tissues.     

In vitro fracture resistance of molar teeth restored with a short fibre-reinforced composite material

Objectives

The purpose of this in vitro study was to evaluate the efficiency of a short fibre-reinforced composite (SFRC) material compared to conventional composites when restoring class II. MOD cavities in molar teeth with different layering techniques.

Methods

One hundred and thirty mandibular third molars were divided into 5 groups (n = 26). Except for the control group (intact teeth), in all other groups MOD cavities were prepared. The cavities were restored by either conventional composite with horizontal and oblique layering or by SFRC with horizontal and oblique layering. The specimens were submitted to static fracture toughness test. Fracture thresholds and fracture patterns were evaluated.

Results

In general, no statistically significant difference was found in fracture toughness between the study groups, except for horizontally layered conventional composite restorations, which turned out to be significantly weaker than controls. However, SFRC yielded noticeably higher fracture thresholds and only obliquely applied SFRC restorations exhibited favourable fracture patterns above chance level.

Conclusions

The application of SFRC did not lead to a statistically significant improvement of the fracture toughness of molar teeth with MOD cavities. Still, SFRC applied in oblique increments measurably reduces the chance of unrestorable fractures of molar teeth with class II MOD cavities.

Clinical significance

The restoration of severely weakened molar teeth with the use of SFRC combined with composite might have advantages over conventional composites alone. It was observed from the statistical data, that the application of SFRC with an oblique layering technique yielded not significantly but better fracture thresholds and more favourable fracture patterns than any other studied material/technique combination. Thus further investigations need to be carried out, to investigate the possible positive mechanical effects of SFRC. The application of the horizontal layering technique with conventional composite materials is inferior to the oblique technique and SFRC materials.     

Crosstalk between cholesterol homeostasis and drug metabolism

Nowadays cardiovascular diseases are among the major causes of mortality in the developed world. High cholesterol level in blood and atherosclerosis play the main role in progression of cardiovascular diseases. Reducing serum cholesterol level has been shown to avoid deleterious effects, whereas in serious diseases it improves the outcome. A widely used, statin-based therapy induces a decrease in de novo cholesterol biosynthesis in the liver. Another possibility for lowering serum cholesterol level is to block the uptake of dietary cholesterol from intestine (e.g. ezetimibe). Coadministration of statins and cholesterol uptake inhibitors provides an efficient therapeutical strategy. Several therapeutic agents, reducing serum cholesterol level, are able to regulate the expression of not only cholesterogenic enzymes, but of the major drug metabolizing enzymes, cytochromes P450. The crosstalk between cholesterol homeostasis and drug metabolism is mediated by nuclear receptors, activating target genes in response of endogenous and exogenous ligands. Better understanding of the crosstalk between cholesterol homeostasis and drug metabolism is essential for developing an adequate strategy in therapy and in novel drug development.     

Vena cava superior syndrome: surgical treatment of the thrombosis of the superior vena cava after implantation of a hemodialysis catheter--a case report and review of the literature

One of the rare reasons of the non malignant superior vena cava syndrome is the thrombosis of superior vena cava. Obstruction or occlusion of central veins is one of the many complications of the more and more frequently used central venous catheters and pacemaker electrodes. The authors report a case of superior vena cava thrombosis resulting in dialysis catheter insufficiency in case of a young, uraemic, female patient wit Tesio catheter and the surgical treatment of it with the use of cardiopulmonary bypass during the operation. Apropos of this case, the authors outline the causes of malignant, non-malignant and iatrogenic superior vena cava syndrome, furthermore the conservative, surgical and catheter therapy of the syndrome.