Effects of combination of cyclosporine with losartan or enalapril on kidney function in uremic rats

Long-term treatment with cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Angiotensin-converting enzyme inhibitors have well-known nephroprotective properties and may prevent cyclosporine A (CYA)-induced hypertension. Angiotensin receptor 1 antagonists have similar properties. The purpose of this study was to investigate if losartan or enalapril could be administered with CYA to reduce its nephrotoxic effect in uremic rats. The studies were performed on the following groups of rats: group I--control; group II--control rats + losartan; group III--control rats + CYA; group IV uremic rats; group V--uremic rats + losartan; group VI--uremic rats + CYA; group VII--uremic rats + losartan + CYA, group VIII--control rats + enalapril; group IX--control rats + enalapril + CYA; group X - uremic rats + enalapril; group XI--uremic rats + enalapril + CYA. Pretreatment with CYA, losartan or enalapril in uremic rats resulted in a significant increase in urea and creatinine levels and a decrease in hematocrit. The same effect was observed when uremic rats were given CYA + losartan or CYA + enalapril. Pretreatment with losartan was associated with the increase in the level of CYA much higher than with CYA treatment alone. Similarly, pretreatment with enalapril resulted in a significant increase in CYA concentration in both groups of rats given CYA: uremic and non-uremic. Results of our study show that the treatment with cyclosporine and a combination of losartan or enalapril results in an increase in creatinine and urea levels and a decrease in hematocrit. Therefore, physicians should exercise caution, when they give losartan and enalapril to kidney allograft recipients treated with cyclosporine, particularly with impaired allograft function.     

Neuroprotective effects of antiepileptic drugs

Experimental and clinical data indicate that epilepsy and seizures lead to neuronal cell loss and irreversible brain damage. This neurodegeneration results not only in the central nervous system dysfunction but may also be responsible for the decreased efficacy of some antiepileptic drugs (AEDs). The aim of this review was to assemble current literature data on neuroprotective properties of AEDs. The list of hypothetical neuroprotectants is long and consists of substances which act via different mechanisms. We focus on AEDs since this heterogeneous group of pharmaceuticals, as far as mechanisms of their action and mechanisms of neuronal death are concerned, should provide protection in addition to antiseizure effect itself. Most studies on neuroprotection are based on animal experimental models of neuronal degeneration. Electrically and pharmacologically evoked seizures as well as different models of ischemia are frequently used. Although our knowledge about properties of AEDs is still not complete and discrepancies occasionally occur, the group seems to be promising in terms of neuroprotection. Some of the drugs, though, turn out to be neutral or even have adverse effects on the central nervous system, especially on immature brain tissue (barbiturates and benzodiazepines). Unfortunatelly, we cannot fully extrapolate animal data to humans, therefore further well designed clinical trials are necessary to determine neuroprotective properties of AEDs in humans. However, there is a hope that AEDs will have a potential to serve as neuroprotectants not only in seizures, but perhaps, in other neurodegenerative conditions in humans as well. The novel AEDs (especially lamotrigine, tiagabine, and topiramate) seem particularly promising.     

Somatostatin analogs in the treatment of carcinoid syndrome: a case report and review of literature

We report the case of 48-year old patient with carcinoid syndrome successfully treated with somatostatin analogues. We also present the review of published literature about the use of somatostatin analogues in the treatment of carcinoid syndrome. In addition, reported case shows difficulties in access to this treatment, caused by economical reasons.     

Evaluation of the effect of deionized water on selected components of fat,carbohydrate, and protein metabolism,morphology and the acid-base equilibrium in the rats blood

By virtue of the carried out experimental investigations no essential effect of deionized water, administered orally for 90 days in a dose ad libitum, has been stated to act, in the blood of rats, on the determined elements of carbohydrate, protein metabolism, on morphology and the peripheral blood smear. The observed value shifts of the indices of fat metabolism and of the acid-base equilibrium are contained within the limits of physiological norms for that species of animals.     

Is there a restless arms syndrome?

Three patients are reported who had painful numbness in upper extremities regressing temporarily after performing rather intensive movements. Analgesics are non efficacious in relieving this symptom. The observed painful syndrome relieved for some time by movements of the upper extremities seems to be an analogy of the restless legs syndrome. Perhaps the designation "restless arms syndrome" could be introduced.     

Concomitant focal fibrocartilaginous dysplasia of the tibia and eosinophilic granuloma of the jaw in a child

This 2-year-old child presented with concomitant eosinophilic granuloma of the lower jaw and focal fibrocartilaginous dysplasia of the right tibia. Her eosinophilic granuloma was diagnosed on the basis of the clinical picture, imaging studies and the characteristic histologic appearance. Focal fibrocartilaginous dysplasia was revealed incidentally during the eosinophilic granuloma staging process. After chemotherapy, all signs of eosinophilic granuloma subsided, but focal fibrocartilaginous dysplasia remained without signs of clinical or radiographic progression. The importance of differentiating these two conditions is stressed in order to avoid ineffective and inappropriate treatment of focal fibrocartilaginous dysplasia.     

Th1/Th2 balance and CD45-positive T cell subsets in primary nephrotic syndrome

T cells are involved in the pathogenesis of nephrotic syndrome (NS). The aim of the study was to determine whether the activity of T-helper-1 (Th1) and T-helper-2 (Th2) cells and the distribution of the lymphocyte subsets, namely CD45RA+CD4+ (”naive” helper T cells, suppressor-inducer), CD45RA+CD8+ (”naive” suppressor T cells, suppressor-effector), CD45RO+CD4+ (”memory” helper T cells), are predictive for steroid sensitivity in children with primary NS. These parameters were assessed at the onset of disease, before initiation of steroid therapy. Two groups of NS children were retrospectively formed according to steroid sensitivity (SS) or resistance (SR). The activity of Th1 and Th2 cells was defined by the production of interleukin-2 (IL-2), interferon-γ, IL-4, and IL-10 in the supernatants of CD4+ T cell cultures activated with autologous monocytes presenting tetanus toxoid (TT). Peripheral lymphocyte subsets were determined using double- or triple-color flow cytometry. In SS children with NS we found a decreased proliferative response of CD4+ T cells to TT stimulation, cytokine synthesis indicating the predominance of Th2 activity, and an increased percentage of activated suppressor-inducer (CD45RA+ CD4+CD25+, 5.18±0.8, P<0.001) and suppressor-effector (CD45RA+CD8+CD25+, 2.05±0.6, P<0.01) cells, with the concomitant reduction of activated memory cells (CD45RO+CD4+CD25+, 0.2±0.1, P<0.001). In children with SRNS we found an increased proliferative response of CD4+ T cells to TT, a rise in activated memory (CD45RO+CD4+CD25+, 3.82±0.7, P<0.01) and suppressor-inducer peripheral T cells (CD45RA+ CD4+CD25+, 3.85±0.6, P<0.01), but a low percentage of activated suppressor-effector (CD45RA+CD8+ CD25+, 0.5±0.2, P<0.05) T cells. We conclude that prior to treatment the distribution of lymphocyte subpopulations in peripheral blood together with Th1 and Th2 cell activity provides a useful tool for evaluating the likelihood of steroid sensitivity in patients with primary NS. Received: 3 November 1998 / Revised: 1 September 1999 / Accepted: 8 September 1999