Effect of the Choice of Primary Chemotherapy on the Cumulative Length of Stay in Hospital for Multiple Myeloma

The actual use of hospital beds for patients with multiple myeloma was calculated from a randomised trial of primary treatment with either melphalan and prednisone (MP, 66 patients) or intensive combination chemotherapy with vincristine, cyclophosphamide, lomustine, melphalan and methylprednisolone (MOCCA, 64 patients). The survival of the patients was similar in both arms, and the samples, 20 and 32 patients, respectively, were well representative for the whole arms. The average numbers of hospital days were similar fur both arms. For the first year MP 33.2 (SD 27.6) vs. MOCCA 32.1 (SD 19.0), and during the first to 4th years 78.5 (SD 45.9) vs. 67.8 (SD 34.1). For the year of death it was 50.4 (SD 33.1) vii. 36.3 (SD 27.0), respectivelly. Thus the choice of primary chemotherapy whether conventional or more aggressive had no influence on the actual number of in-patient hospital days concerned. When the combination chemotherapy schedule is well tolerated it can be administered just as well on an ambulatory basis or by using it with very short admissions. It seems that the need for inpatient care for patients with multiple myeloma is mostly related to the complications of the disease itself and to intercurrent disorders including infections.     

Cardiovascular safety and benefits of GLP-1 receptor agonists

Introduction: Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) constitute a class of drugs for the treatment of type 2 diabetes, and currently, six different GLP-1RAs are approved. Besides improving glycemic control, the GLP-1RAs have other beneficial effects such as weight loss and a low risk of hypoglycemia. Treatment with the GLP-1RA lixisenatide has been shown to be safe in patients with type 2 diabetes and recent acute coronary syndrome. Furthermore, liraglutide and semaglutide have been shown to reduce cardiovascular (CV) disease (CVD) risk in type 2 diabetes patients with established and/or high risk of CVD. The CV safety of the remaining GLP-1RAs in type 2 diabetes patients with established and/or high risk of CVD remains uncertain, but ongoing CV outcome trials (CVOTs) will elucidate this within a few years.

Areas covered: The aim of this review is to provide an overview of the existing GLP-1RAs with a particular focus on their clinical effects on CV risk factors and their CV safety and benefits.

Expert opinion: Data on the CV risks and benefits associated with GLP-1RA treatment in patients with type 2 diabetes and high risk of CVD are emerging – and look promising (especially for liraglutide and semaglutide). Data from ongoing CVOTs will be crucial for the positioning of the individual GLP-1RAs in the treatment of patients with type 2 diabetes and high risk of CVD. However, the long-term CV safety and the potential of GLP-1RAs to prevent CVD in type 2 diabetes patients with less risk of CVD (e.g. newly diagnosed patients) remain uncertain.     

Clinical pharmacology of imeglimin for the treatment of type 2 diabetes

ABSTRACT

Introduction

With the rising prevalence of type 2 diabetes (T2D), there is a substantial interest in novel, glucose-lowering drugs that may complement existing treatment options. Imeglimin is an oral antidiabetic agent currently in clinical development.     

Protective effects of tadalafil on experimental spinal cord injury in rats

Tadalafil is a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Nitric oxide (NO) functions as a retrograde neurotransmitter in the spinal cord, and postsynaptic structures respond to NO by producing cGMP. The concentrations of cGMP in the spinal cord are controlled by the actions of PDE. The aim of the study was to evaluate and compare the effects of the use of both methylprednisolone and tadalafil on serum and tissue concentrations of NO, malondialdehyde (MDA) levels, superoxide dismutase (SOD) activity, and tissue glutathione peroxidase (GSH-Px) activity in rats with spinal cord injury (SCI). SCI was induced in Wistar albino rats by dropping a 10 g rod from a 5.0 cm height at T8–10. The 28 rats were randomly divided into four equal groups: tadalafil, methylprednisolone, non-treatment and sham groups. Rats were neurologically tested at 24 hours after trauma. At the end of the experiment, blood samples were collected and spinal cord tissue samples were harvested for biochemical evaluation. The tissue level of NO was increased in the tadalafil group compared with the non-treatment and methylprednisolone groups (p < 0.05). The tissue levels of SOD and GSH-Px did not differ between the groups. Serum levels of NO were higher in the tadalafil group than in the non-treatment group (p < 0.05). The increase in serum SOD levels was greater in the tadalafil group than the methylprednisolone group. Serum MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group (p > 0.05). Tissue MDA levels in the tadalafil and methylprednisolone groups tended to be lower than in the non-treatment group and sham groups (p > 0.05). Although there was no difference in neurological outcome scores between the tadalafil, methylprednisolone and non-treatment groups (p > 0.05), the animals in the tadalafil and methylprednisolone groups tended to have better scores than the non-treatment group. Thus, tadalafil appears to be beneficial in reducing the effects of injury to the spinal cord by increasing tissue levels of NO and serum activity of SOD.     

Macrophage migration inhibitory factor in patients with vitiligo and relationship between duration and clinical type of disease

Background. Vitiligo is a disorder of pigmentation characterized by the presence of depigmented skin macules. Cellular immunity is known to have a role in the pathogenesis of vitiligo. Macrophage migration inhibitory factor (MIF) is a potent activator of macrophages and is considered to play an important role in cell‐mediated immunity. Aims. To determine serum level of MIF in patients with vitiligo and compare with healthy controls. We also aimed to determine whether there is a relationship between MIF levels and the disease duration, clinical vitiligo and involved body surface area (BSA) in patients with vitiligo. Methods. The study group comprised 30 patients with vitiligo (14 men, 16 women) and 30 healthy controls, matched for age and gender. Blood samples were taken for MIF analysis. Results. The mean serum level of MIF in patients with vitiligo (40.83 ± 31.66 pg/mL) was significantly higher than that of the control group (21.00 ± 6.48 pg/mL) (P = 0.002). There was a positive correlation between disease duration and MIF levels (r = 0.601, P < 0.001). Mean MIF level of patients with acral and acrofacial vitiligo (n = 6) was 48.25 ± 32.02 pg/mL, and of patients generalized vitiligo (n = 18) was 44.46 ± 35.25 pg/mL. There was no significant difference between these two groups (P > 0.05). However there was a significant difference in MIF levels between patients with localized (20.41 ± 5.23, n = 5) and acral–acrofacial (P = 0.02) vitiligo and those with generalized (P = 0.006) vitiligo. There was no relationship between BSA and MIF levels. Conclusions. Mean serum MIF level of patients with vitiligo was higher than that of controls, indicating that MIF has a role in the pathogenesis of vitiligo.     

Quantitative determination of ambroxol in tablets by derivative UV spectrophotometric method and HPLC

A derivative UV spectrophotometric method for the determination of ambroxol in tablets was developed. Determination of ambroxol in tablets was conducted by using first-order derivative UV spectrophotometric method at 255 nm (n = 5). Standards for the calibration graph ranging from 5.0 to 35.0 microg/ml were prepared from stock solution. The proposed method was accurate with 98.6+/-0.4% recovery value and precise with coefficient of variation (CV) of 1.22. These results were compared with those obtained by reference methods, zero-order UV spectrophotometric method and reversed-phase high-performance liquid chromatography (HPLC) method. A reversed-phase C(18) column with aqueous phosphate (0.01 M)-acetonitrile-glacial acetic acid (59:40:1, v/v/v) (pH 3.12) mobile phase was used and UV detector was set to 252 nm. Calibration solutions used in HPLC were ranging from 5.0 to 20.0 microg/ml. Results obtained by derivative UV spectrophotometric method was comparable to those obtained by reference methods, zero-order UV spectrophotometric method and HPLC, as far as ANOVA test, F(calculated) = 0.762 and F(theoretical) = 3.89, was concerned.     

Serum iron,zinc and copper levels and lipid peroxidation in children with chronic giardiasis

This study investigated the levels of iron, zinc, and copper and their demolishing effects against lipid peroxidation in chronic giardiasis. Serum iron, zinc and copper levels, erythrocyte cytosolic superoxide dismutase activity, and malondialdehyde levels were measured in 34 children with chronic giardiasis and were compared with controls. The serum iron and zinc levels and erythrocyte superoxide dismutase activity were significantly lower, and malondialdehyde levels were significantly higher among the children with chronic giardiasis compared to the control group (p < 0.001). There was no significant difference in copper levels between the two groups (p > 0.05). Consequently, the oxidant-antioxidant balance may tilt towards the oxidative side due to weakness of the antioxidant system in giardiasis. If early and proper treatment is not performed, free radical-mediated damage might occur in children with chronic giardiasis.     

Liraglutide changes postprandial responses of gut hormones involved in the regulation of gallbladder motility

Aim

Liraglutide treatment is associated with gallbladder-related disorders and has been shown to delay postprandial gallbladder refilling. The gut hormones cholecystokinin (CCK), fibroblast growth factor 19 (FGF19) and glucagon-like peptide 2 (GLP-2), are known to regulate gallbladder motility and may be implicated in gallbladder-related disorders associated with liraglutide treatment.

Materials and Methods

In a double-blind, 12-week trial, 52 participants [50% male, age 47.6 ± 10.0 years, body mass index 32.6 ± 3.4 kg/m² (mean ± standard deviation)] with obesity were randomized 1:1 to once-daily subcutaneous liraglutide (escalated from 0.6 mg to 3.0 mg once-daily) or placebo. During liquid meal tests performed at baseline, after the first dose and following 12 weeks of treatment, we evaluated postprandial gallbladder dynamics and plasma responses of CCK, FGF19 and GLP-2.

Results

Liraglutide reduced postprandial FGF19 after the first dose [area under the curve (AUC)_{0-240 min} 24.8 vs. 48.0 min × ng/ml, treatment ratio (TR) (95% confidence interval) 0.52 (0.39; 0.69)] and following 12 weeks of treatment [AUC_{0-240 min} 33.7 vs. 48.5 ng/ml × min, TR 0.69 (0.52; 0.93)]. Liraglutide also reduced postprandial GLP-2 responses (AUC_{0-240 min} 3650 vs. 4894 min × pmol/L, TR 0.75 (0.62; 0.90)] following the first dose as well as after 12 weeks [AUC_{0-240 min} 3760 vs. 4882 min × pmol/L, TR 0.77 (0.60; 0.99)]. Liraglutide increased postprandial responses of CCK after the first dose [AUC_{0-240 min} 762 vs. 670 min × pmol/L; TR 1.14 (0.97; 1.33)] and following 12 weeks of treatment [AUC_{0-240 min} 873 vs. 628 min × pmol/L; TR 1.39 (1.12; 1.73)].

Conclusion

Compared with placebo, treatment with liraglutide decreased postprandial FGF19 and GLP-2 concentrations and increased postprandial CCK concentrations, which may explain the delayed postprandial gallbladder refilling observed in individuals with obesity treated with liraglutide.     

The relationship between vitamin D and disease activity and functional health status in rheumatoid arthritis

We aimed to establish the relationship between serum vitamin D levels and disease activity and health status in rheumatoid arthritis. Sixty-five patients with RA fulfilling ACR criteria for the classification of rheumatoid arthritis and forty healthy controls were included in this study. Disease activity was assessed according to the Disease Activity Score including 28 joint counts. C-reactive protein (CRP, mg/dl) was determined by the nephelometric method. Erythrocyte sedimentation rate (ESR, mm/h) was determined by the Westergren method. Rheumatoid factor (RF, IU/ml) was also determined by the nephelometric method, and RF > 20 IU/ml was defined as positive. 25-OH Vitamin D EIA Kit was used to measure serum 25-OH Vitamin D levels. We found that the mean of the 25-OH D vitamin levels of the patients with RA was not different than that of controls (P = 0.936). We divided patients with RA into three groups according to DAS28 as low activity group (group 1, n = 25), moderate activity group (group 2, n = 25), and high activity group (group 3, n = 15). 25-OH vitamin D levels of the patients in the high activity group (group 3) were found to be the lowest (P < 0.001), and the patients with moderate disease activity had lower levels than those in the mild group (P = 0.033). Serum 25-OH vitamin D levels were significantly negatively correlated with DAS28, CRP, and HAQ (respectively, r = −0.431, P = 0.000, r = −0.276, P = 0.026, and r = −0.267, P = 0.031). Serum vitamin D levels in patients with RA were similar those in the healthy controls, while it significantly decreases in accordance with the disease activity and decreasing functional capacity.