Tacrolimus and quality of life after kidney transplantation--a multicenter study

Kidney transplantation is currently the treatment of choice for end-stage renal disease. Although new immunosuppressive drugs have been introduced into clinical practice, the effect of such medication on quality of life (QoL) in transplant recipients is still unclear. The present study analyzes the impact of tacrolimus-based immunosuppression on QoL in a representative sample of adult kidney transplant recipients from Rio Grande do Sul, a Brazilian southern state. This was a cross-sectional multicenter study which used the SF-36 Health Survey for measuring QoL. The effect of tacrolimus on QoL was adjusted for possible confounders using multiple linear regression. A total of 272 patients (from 11 different centers) were evaluated, 48 of them were treated with tacrolimus. Transplant patients in use of tacrolimus presented significant higher scores in the physical component summary of SF-36 than non-users (49.1+/-8.3 vs. 46.1+/-8.7; p=0.03), and such difference was noted in the physical functioning and general health subscales (81.5+/-17.1 and 74.7+/-21.8; 74.6+/-22.3 and 67.1+/-22.3 for users and non-users of tacrolimus, respectively, p<0.05). The effect of tacrolimus remained significant after adjustment for age, gender, skin color and time since transplantation (coeff.: 2.83; 95% CI: 0.05-5.6, p=0.045). The association between tacrolimus-based immunosuppression and better perception of physical functioning and general health for renal transplant patients represents a significant finding as it may influence therapeutical decisions and contribute to maximize kidney transplantation benefits.     

Epidemiologic and laboratory assessments of etiologic implications of Blastocystis hominis in gastrointestinal diseases

Authors present the first laboratory and epidemiological results which reveal the circulation in a population of protozoan Blastocystis hominis and its implication in the determinations of some gastrointestinal troubles, with fever, diarrhea and constipation, intense intestinal meteorism, associated with abdominal pain and cramps. Out of the 3106 investigated patients, 9.7% presented B. hominis as a unique etiologic agent, with an increased prevalence in adults (74.3%) and women (65.3%). Blastocystis infection with clinical manifestations or its asymptomatic form is included among emergent diseases.     

Development of peritoneal dialysis at Rijeka Clinical Hospital Center

The dialysis population is steadily rising as a consequence of the growing incidence of terminal renal failure patients and lack of organs for transplantation. Peritoneal dialysis (PD) has become an established form of renal replacement therapy. The development of new methods, techniques, PD fluids and catheters has significantly lowered the incidence of complications and increased the use of PD throughout the world. The development of PD at Rijeka University Hospital Center, the incidence of PD patients, their underlying renal disease leading to terminal renal failure, demographic characteristics of patients, complications of treatment, and causes of discontinuation of PD treatment are described. At Rijeka University Hospital Center, PD was introduced in 1963 in patients with acute renal failure (ARF), and in 1965 in patients with chronic renal failure (CRF). Until June 2002, 149 patients were treated, 71 with ARF and 78 with CRF. Continuous peritoneal dialysis was introduced at our hospital in 1978. An increasing number of patients on continuous ambulatory peritoneal dialysis (CAPD), altogether 35, was noticed in 1999. Automated peritoneal dialysis (APD) was introduced in January 2001. Five patients were treated with this method until June 2002. The most common underlying renal diseases in patients treated from January 1999 until June 2002 were diabetic nephropathy in 13 (37.1%) and glomerulonephritis in 11 (31.4%) patients, mean age 55.5 years, range 31-75 years, both sexes equally present. The leading cause of complications were infections and the main cause of death was cardiovascular disease. Five (14.3%) patients received kidney transplants which have been functioning well in all of them. Because of the high incidence of complications during the seventies, intermittent peritoneal dialysis (IPD) was used only occasionally. A significant increase in the number of patients on CAPD was observed in 1999. By the end of 2001 almost ten percent of patients receiving dialytic treatment were on CAPD. The most common complications were peritoneal catheter exit site infection and peritonitis, which caused referral to HD treatment in four (11.4%) and death in two (5.7%) patients with impossible vascular access. The knowledge and availability of different renal replacement therapies allow the choice and application of the most appropriate treatment option in individual patients with terminal renal failure. In comparison to HD, PD improves the quality of patient's life and decreases mortality in the first years of treatment. Patients with cardiovascular disease and diabetes, whose incidence is steadily rising, have a higher incidence of complications on hemodialysis treatment. In these patients PD is preferred, especially if used as the first dialytic treatment modality. PD has also provided a means of managing patients with no possibility for vascular access for HD treatment. Infective and mechanical complications are the main obstacles during PD treatment. Adequate facilities, equipment, educated and well-trained medical personnel and appropriate selection and thorough education of patients are necessary for a successful PD program.     

Therapeutic potential of ERK5 targeting in triple negative breast cancer

Triple negative breast cancers (TNBCs) account for 15% of all breast cancers, and represent one of the most aggressive forms of the disease, exhibiting short relapse-free survival. In contrast to other breast cancer subtypes, the absence of knowledge about the etiopathogenic alterations that cause TNBCs force the use of chemotherapeutics to treat these tumors. Because of this, efforts have been devoted with the aim of incorporating novel therapies into the clinical setting. Kinases play important roles in the pathophysiology of several tumors, including TNBC. Since expression of the MAP kinase ERK5 has been linked to patient outcome in breast cancer, we analyzed the potential value of its targeting in TNBC. ERK5 was frequently overexpressed and active in samples from patients with TNBC, as well as in explants from mice carrying genetically-defined TNBC tumors. Moreover, expression of ERK5 was linked to a worse prognosis in TNBC patients. Knockdown experiments demonstrated that ERK5 supported proliferation of TNBC cells. Pharmacological inhibition of ERK5 with TG02, a clinical stage inhibitor which targets ERK5 and other kinases, inhibited cell proliferation by blocking passage of cells through G₁ and G₂, and also triggered apoptosis in certain TNBC cell lines. TG02 had significant antitumor activity in a TNBC xenograft model in vivo, and also augmented the activity of chemotherapeutic agents commonly used to treat TNBC. Together, these data indicate that ERK5 targeting may represent a valid strategy against TNBC, and support the development of trials aimed at evaluating the clinical effectiveness of drugs that block this kinase.     

Repeated administration of an aqueous spray-dried extract of the leaves of Passiflora alata Curtis (Passifloraceae) inhibits body weight gain without altering mice behavior

Ethnopharmacological relevance

Passiflora alata is a Southern American species that constitutes many traditional remedies as well as phytomedicines used for sedative and anxiolytic purposes in Brazil. However studies on repeated treatment effects are scarce.

Aim of the study

To evaluate behavioral, physiological and biochemical effects of the repeated treatment with an aqueous spray-dried extract of Passiflora alata leaves containing 2.5% (w/v) of flavonoids (PA) in mice.

Material and methods

Male adult CF1 mice were treated (p.o.) for 14 days with PA (2.5; 25 or 250 mg/kg). The feeding behavior was evaluated at the beginning (1 h after the first administration) and at the end of the treatment (15th day). The body weight gain and food consumption were monitored along the days. On day 15 mice were evaluated on plus maze, spontaneous locomotor activity, catalepsy and barbiturate sleeping time tests. Serum glucose, lipids, ALT and AST enzymes were determined. Liver, kidney, perirenal fat, epididymal and peritoneal fat were analyzed.

Results

The repeated treatment with the highest dose tested (250 mg/kg) did not alter the mice behavior on open field, elevated plus maze, catalepsy and barbiturate sleeping time tests. Repeated administration of PA 250 decreased mice feeding behavior and weight gain. PA 25 and PA 250 reduced mice relative liver weight and caused mild hepatic hydropic degeneration as well as a decrease in alanine aminotransferase (ALT) serum level.

Conclusions

These results indicate that Passiflora alata does not present central cumulative effects and point to the needs of further studies searching for its hepatotoxicity as well as potential anorexigenic.     

Porous Semi‐Interpenetrating Hydrogel Networks Based on Dextran and Polyacrylamide With Superfast Responsiveness

AAm was free‐radical polymerized at various temperatures in the presence of N,N'‐methylenebisacrylamide as a cross‐linker and dextran resulting in novel Dx/PAAm semi‐IPNs. The structure and morphology of networks were investigated by means of FTIR, DSC, and ESEM. In comparison to the PAAm network, the interior network structures of the novel semi‐IPNs prepared at ?18 °C exhibit a heterogeneous morphology consisting of pores of sizes about 80 µm, while those formed at +5 and +25 °C have pores with sizes about 3 µm. The Dx/PAAm semi‐IPNs exhibited higher swelling ratios, than those without Dx, irrespective of the gel preparation temperature. Moreover, Dx/PAAm semi‐IPN hydrogels formed at ?18 °C attain the equilibrium state in water within 15 s.