Biological Drugs: Classic Adverse Effects and New Clinical Evidences

The last 20 years was characterized by great improvements in the efficacy and tolerability of anticancer therapies. Most of these changes are related to the introduction of targeted drugs, which presents a better activity on the biology of cancer and less toxicity. Nevertheless, the initial enthusiasm was cooled by the emerging evidences of cardiac side effects. The aim of this review is to describe the actual knowledge about the possible cardiotoxicity of targeted drugs. The most important need is the detection of early cardiotoxicity and the evidence of subtle myocardial dysfunction that allows to begin a protective therapy. In our review we analyzed the non invasive imaging techniques to early predict myocardial dysfunction. Echocardiography seems to be the ideal method for her availability, safety and clinical usefulness, in particular the new echocardiographic techniques like speckle tracking.     

Oxytocin promotes bone formation during the alveolar healing process in old acyclic female rats

ObjectiveOT was reported to be a direct regulator of bone mass in young rodents, and this anabolic effect on bone is a peripheral action of OT. The goal of this study was to investigate the peripheral action of oxytocin (OT) in the alveolar healing process in old female rats.Materials and methodsFemales Wistar rats (24-month-old) in permanent diestrus phase, received two ip (12 h apart) injections of saline (NaCl 0.15 M – control group) or OT (45 μg/rat – treated group). Seven days later, the right maxillary incisor was extracted and analyses were performed up to 28 days of the alveolar healing process (35 days after saline or OT administration).ResultsCalcium and phosphorus plasma concentrations did not differ between the groups. The plasma biochemical bone formations markers, alkaline phosphatase (ALP) and osteocalcin were significantly higher in the treated group. Histomorphometric analyses confirmed bone formation as the treated group presented the highest mean value of post-extraction bone formation. Tartrate-resistant acid phosphatase (TRAP) was significantly reduced in the treated group indicating an anti-resorptive effect of OT. Immunohistochemistry reactions performed in order to identify the presence of osteocalcin and TRAP in the bone cells of the dental socket confirmed these outcomes.ConclusionsOT was found to promote bone formation and to inhibit bone resorption in old acyclic female rats during the alveolar healing process.     

Spermatogonial survival after cryopreservation and short-term orthotopic immature human cryptorchid testicular tissue grafting to immunodeficient mice

BACKGROUND: Fertility preservation has become an urgent clinical requisite for prepubertal male cancer patients undergoing gonadotoxic treatment. As these patients do not yet produce spermatozoa for freezing, only immature tissue is available for storage. We studied the survival and proliferative activity of spermatogonia and Sertoli cells after cryopreservation of cryptorchid testicular tissue pieces followed by xenografting for 21 days. METHODS AND RESULTS: Single pieces of tissue from cryptorchid testes (2-9 mm(3)) of young boys (2-12 years) were cryopreserved, thawed and transplanted into the scrotum of mice. Quantitative morphometric and immunohistochemical techniques were used to evaluate the integrity of the tissue, as well as the survival and proliferative capacity of spermatogonia and Sertoli cells before and after freezing/thawing/grafting. Three weeks after grafting, cryopreserved tissue was removed and analysed. Most of the tubules (88.3%) were intact and there was no fibrosis or sclerosis, 14.5% of the initial spermatogonial population remained, as identified by the MAGE A4 antibody, and 32% of these cells showed proliferative activity evidenced by Ki67, compared to 17.8% before cryopreservation and grafting. The number of Sertoli cells was unchanged and 5.1% were Ki67-positive, compared to none at all before freezing and grafting. CONCLUSIONS: Through our orthotopic xenografting model, we have demonstrated the survival and proliferative activity of spermatogonia and Sertoli cells in cryopreserved immature human cryptorchid tissue. Testicular tissue banking may thus prove to be a promising technique for the preservation of fertility in prepubertal boys undergoing oncological treatments. As the stem cell niche is maintained, the cryopreserved tissue can potentially be used for future autotransplantation. In addition, whole tissue freezing does not exclude alternative clinical uses, including isolated cell transplantation after dissociation, selection and enrichment. However, as this work was done on cryptorchid tissue, studies on normal immature testicular tissue, involving longer grafting periods, are needed to demonstrate a differentiation capacity before clinical implementation. Ethical and safety issues should also be addressed.     

DOUBLE-BLIND PROSPECTIVE RANDOMIZED STUDY COMPARING POLYETHYLENE GLYCOL TO LACTULOSE FOR BOWEL PREPARATION IN COLONOSCOPY

Background

Colonoscopy is the most frequent exam used to evaluate colonic mucosa, allowing the diagnosis and treatment of many diseases. The appropriate bowel preparation is indispensable for the realization of colonoscopy. Therefore, it is necessary the use of laxative medications, preferentially by oral administration.

Aim

To compare two medications used in bowel preparation in adult patients going to ambulatory colonoscopy and to analyze the patients'' profile.

Methods

A double-blind prospective study with 200 patients, randomized in two groups: one that received polyethilene glycol and another that received lactulose. The patients answered to questionnaires to data compilation, as tolerance, symptoms and complications related to preparation. Besides, it was also evaluated the prepare efficacy related to the presence of fecal residue.

Results

Intestinal habit alterations and abdominal pain were the main reasons to realize the exams and hypertension was the most prevalent comorbidity. Ten percent of the ones who received lactulose didn''t get to finish the preparation and 50% considered the taste "bad, but tolerable". The most common subjective symptom after the medication was nausea, especially after lactulose. During the exam, most of the patients who used lactulose had a "light discomfort" and the ones who used polyethilene glycol considered the discomfort as "tolerable". The quality of the preparation was good in 75%, undependable of the medication that was used.

Conclusion

Polyethilene glycol was more tolerable when compared to lactulose, without difference on the quality of the preparation.     

Effects of laser irradiation (670-nm InGaP and 830-nm GaAlAs) on burn of second-degree in rats

This study investigated the effects of 670-nm indium gallium phosphide (InGaP) and 830-nm gallium aluminum arsenide (GaAlAs) laser therapy on second-degree burns induced on the back of Wistar rats. Sixty-three male Wistar rats were anesthetized, and second-degree burns were made on their back. The animals were then divided randomly into three groups: control (C), animals treated with 670-nm InGaP laser (LIn), and animals treated with 830-nm GaAlAs laser (LGa). The wound areas were removed after 2, 6, 10, 14, and 18 days of treatment and submitted to structural and morphometric analysis. The following parameters were studied: total number of granulocytes and fibroblasts, number of newly formed blood vessels, and percentage of birefringent collagen fibers in the repair area. Morphometric analysis showed that different lasers 670-nm InGaP and 830-nm GaAlAs reduced the number of granulocytes and an increase of newly formed vessels in radiated lesions. The 670-nm InGaP laser therapy was more effective in increasing the number of fibroblasts. The different treatments modified the expression of VEGF and TGF-β1, when compared with lesions not irradiated. The different types of light sources showed similar effects, improved the healing of second-degree burns and can help for treating this type of injury. Despite the large number of studies with LLTI application in second-degree burns, there is still divergence about the best irradiation parameters to be used. Further studies are needed for developing a protocol effective in treating this type of injury.     

Patient- and Provider-Reported Information about Transplantation and Subsequent Waitlisting

Because informed consent requires discussion of alternative treatments, proper consent for dialysis should incorporate discussion about other renal replacement options including kidney transplantation (KT). Accordingly, dialysis providers are required to indicate KT provision of information (KTPI) on CMS Form-2728; however, provider-reported KTPI does not necessarily imply adequate provision of information. Furthermore, the effect of KTPI on pursuit of KT remains unclear. We compared provider-reported KTPI (Form-2728) with patient-reported KTPI (in-person survey of whether a nephrologist or dialysis staff had discussed KT) in a prospective ancillary study of 388 hemodialysis initiates. KTPI was reported by both patient and provider for 56.2% of participants, by provider only for 27.8%, by patient only for 8.3%, and by neither for 7.7%. Among participants with provider-reported KTPI, older age was associated with lack of patient-reported KTPI. Linkage with the Scientific Registry for Transplant Recipients showed that 20.9% of participants were subsequently listed for KT. Patient-reported KTPI was independently associated with a 2.95-fold (95% confidence interval [95% CI], 1.54 to 5.66; P=0.001) higher likelihood of KT listing, whereas provider-reported KTPI was not associated with listing (hazard ratio, 1.18; 95% CI, 0.60 to 2.32; P=0.62). Our findings suggest that patient perception of KTPI is more important for KT listing than provider-reported KTPI. Patient-reported and provider-reported KTPI should be collected for quality assessment in dialysis centers because factors associated with discordance between these metrics might inform interventions to improve this process.