Effect of excess dietary copper on proliferation and differentiation of the proerythroblasts and erythrocytes in rats

This research was carried out to test the cytotoxic effects of excess copper in rats. Animals were divided into three groups, each containing five animals. Low dose (2 mg/kg) and high dose (4 mg/kg) of copper sulphate were force-fed into the animal by a stomach tube daily for 3 weeks and the third group was used as the control. At the end of each week, three animals (one of each group) were randomly selected and sacrificed. Blood samples were collected and blood smears were made. The bone marrow was collected from the heads of long-bones and bone marrow smears were also prepared. It was found that the application of copper sulphate doses modulates the proliferation and differentiation of stem cell progenitors and erythrocytes. Several alterations were observed and these were time- and dosedependent. Of these alterations, the predominant existence of giant pro-erythroblasts and promyeloblasts marked the increase of adipose cells and degeneration of pro-erythroblasts among the bone marrow cells. Also observed were hypochromia, anisocytosis, fragmentation and burr-shaped erythrocytes.Key words: Environmental pollution, copper toxicity, stem cells, blood, rats

In vitro cytotoxicity and induction of apoptosis by multiwalled carbon nanotubes in human peripheral lymphocytes: Correlation with physicochemical properties

Multiwalled carbon nanotubes (MWCNTs) consist of more than 80% of the current nanomaterials’ applications worldwide. Despite their wide application, little information is known concerning their impact on human health. The current study aims to identify the in vitro effects of exposure of the human peripheral blood lymphocytes (PBL) to MWCNTs and the possible associations with their physiochemical properties. Two doses (50 and 500 µg/ml) of four different commercially available MWCNTs (obtained from Frascati Laboratory, Sigma Co., Sun Nanotech Co. and Shenzhen Co.) were used in this study. Cell viability and apoptotic activity were evaluated by trypan blue exclusion test and Annexin-V/PI staining in peripheral blood leukocytes (PBL). Physicochemical properties of the different MWCNTs were determined and correlated with the cytotoxicity results after exposure for 12 and 48 h. Results indicate that PBL exposed to MWCNTs showed decreased cell viability and increased apoptosis in a dose- and time-dependent manner. The Pearson’s correlation test showed a lack of relationship between diameter of nanoparticles and their pro-apoptotic activity (r2= 0.282), whereas significant correlations were found between pro-apoptotic activity and the presence of some metal contaminants such as nickel, cobalt and gold (r2= 0.919, 0.698 and 0.520, respectively). Our results therefore suggest that carbon nanotubes at high concentrations lowered cell viability in vitro and induced apoptosis in human cells in vitro. In addition, the results indicate that metal contaminants in carbon nanotubes may be causative of some of the adverse outcomes observed. Finally, our finding provides important information on the biohazard potential of some carbon nanotubes in humans.Key words: Multiwalled, carbon, nanotubes, cytotoxicity, apoptosis, flow cytometry, viability,  lymphocytes

The possible protective effect of L-arginine against 5-fluorouracil-induced nephrotoxicity in male albino rats

5-fluorouracil (5-FU) is a potent antineoplastic agent used for the treatment of various malignancies. The L-arginine nitric oxide (NO) pathway involved in the pathogenesis of chemotherapy induced kidney damage. This work investigated the beneficial mechanism of L-arginine supplementation in 5-FU induced nephropathy. Eighty male Wistar rats were divided into four equal groups: control group; L-arginine group (378 mg/rat/day for 4 weeks); 5-FU group (189 mg/rat/week for 4 weeks) and L-arginine for 1 week before and 4 weeks concomitant with 5-FU group. At the end of experiment, the kidney functions were assessed and kidneys specimens were processed for paraffin sections and stained with haematoxylin and eosin (H&E), Masson’s trichome (MT) and periodic acid-Schiff (PAS) stains. Other sections were processed for immunohistochemical demonstration of caspase-3 and inducible NO synthase (iNOS). Image analyser was used to analyse the results morphometrically and statistically. L-arginine administration to 5-FU treated animals elicited significant reduction in serum urea and creatinine levels, urine volume, urinary protein excretion and kidney/body weight ratio in comparison to fluorouracil treated group. L-arginine improved glomeruloscelerosis, degeneration of convoluted tubules and interstitial fibrosis in 5-FU treated animals. L-arginine attenuated effectively some biochemical and histological changes in 5-FU nephrotoxicity

Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto, Canada

Amikacin; NTM lung disease; Nontuberculous mycobacteriaAmikacina; Malaltia pulmonar per micobacteri no tuberculós; Micobacteri no tuberculósAmikacina; Enfermedad pulmonar por micobacteria no tuberculosa; Micobacteria no tuberculosaBACKGROUND: Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. METHODS: We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. RESULTS: A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. CONCLUSIONS: Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

Safety and effectiveness of low-dose amikacin in nontuberculous mycobacterial pulmonary disease treated in Toronto

Treatment guidelines suggest either a low-dose or high-dose approach when prescribing amikacin for nontuberculous mycobacterial pulmonary disease (NTM PD), but data supporting the low-dose approach are limited. The purpose of this study was to describe the safety and efficacy of the use of a low-dose of intravenous amikacin in a cohort of patients with NTM PD. We retrospectively reviewed all patients with NTM PD who received amikacin at our institution between July 1, 2003 and February 28, 2017. Demographics, clinical, microbiological and radiological data, indication and dose of amikacin, and adverse drug effects were recorded. A total of 107 patients received a regimen containing amikacin for a median (IQR) of 7 (4-11) months. Seventy (65.4%) were female and the mean age (SD) was 58.3 (14.9) years. Amikacin was started at a median dose of 9.9 (2.5) mg/kg/day. Ototoxicity was observed in 30/77 (39%) patients and it was related to female sex (OR 4.96, 95%CI 1.24-19.87), and total dose of amikacin per bodyweight (OR 1.62, 95%CI 1.08-2.43). Patients of East Asian ethnicity were less likely to develop ototoxicity (0.24, 95%CI 0.06-0.95). Out of 96 patients who received amikacin for more than 3 months, 65 (67.7%) experienced symptom improvement and 30/62 (49.2%) converted their sputum to culture negative within a year. Patients with NTM PD treated with low-dose intravenous amikacin frequently developed ototoxicity, which was associated with female sex, and total dose of amikacin per bodyweight. Physicians should carefully consider dose, treatment duration, and long term prognosis in balancing risks and benefits of intravenous amikacin in NTM PD

SYNERGISTIC ANTIOSTEOPOROTIC EFFECT OF LEPIDIUM SATIVUM AND ALENDRONATE IN GLUCOCORTICOID-INDUCED OSTEOPOROSIS IN WISTAR RATS

Bisphosphonates (BP) therapy is a vital option to reduce the risk of bone fracture in people who have osteoporosis. However, Bisphosphonate have displayed several side effects. Lepidium sativum (LS) plant and seeds has been used in traditional folk medicine as a mediator for bone fractures. Therefore, we aimed to compare the biochemical effects of LS alone (2% LS in diet, n=8), BP (Alendronate, 70 mg/kg s.c.; n=8) alone, or LS and BP combined in a rat model of glucocorticoid-induced osteoporosis (GIO) by injecting methylprednisolone 3.5 mg/kg per day for 4 weeks. Serum calcium (Ca), albumin, phosphorus (PO4), bone-specific alkaline phosphatase (b-ALP), and tartrate-resistant acid phosphatase (TRAP) were measured 4 weeks after induction of GIO. GIO-group showed significantly increased serum TRAP and decreased b-ALP. GIO-group also showed significantly decreased serum PO4 and unaltered Ca concentrations. Histological examination of GIO-group tibia bones indicates an osteoporotic changes and a concomitant decrease in percentage of trabecular area/bone marrow area (PTB) in the proximal femoral epiphysis. Treatment with either LS and/or BP ameliorated the above mentioned changes with variable degrees; with a net results of enhanced serum calcium, bone architecture, PTB, b-ALP and decreased TRAP in LS and LS+BP groups compared to that of animals treated with Alendronate alone. In conclusion, our findings present evidence supporting the potential benefits of LS in reducing the burden of GCs on bone health