Direct cost of hysterectomy: comparison of robotic versus other routes

Journal of Robotic Surgery - The aim of this study was to investigate the direct cost of robotic hysterectomy in comparison with abdominal, vaginal, and laparoscopic routes past the initial...     

Synthesis and biological evaluation of pyrrole-2-carboxamide derivatives: oroidin analogues

The reaction of pyrrole or dibromopyrrole-2-trichloroacetone with various amines results in the series of novel pyrrole-2-carboxamide bearing aromatic heterocycle or aryl or alkyl groups. Synthesized molecules were evaluated for their in vitro antibacterial activities. Most of the compounds exhibited potent activity against both Gram-positive and negative pathogens.     

Quantifying subjective assessment of sleep quality, quality of life and depressed mood in children with enuresis

Aim

The aim of this study was to compare a group of children who has monosymptomatic nocturnal enuresis (MNE) with a healthy control group by assessing their depression scales, quality of life and sleep quality.

Methods

Hundred and one children with MNE and 38 healthy controls are included in the study, aged between 8 and 16 years old. All participants were performed the Pediatric Quality of Life Inventory (PedsQL 4.0), Depression Scale for Children (CES-DC) and The Pittsburgh Sleep Quality Index (PSQI) tests. The two groups were compared for their demographic factors and for the results of the tests above.

Results

There were no significant differences between the two groups according to age, gender and other demographic factors. Quality of life, depression and sleep quality scores implied worse health in the patient group. The PedsQL scores were assessed as 1,659.90 ± 296.01 in the patient group and 1,818.42 ± 227.92 in the control group (p = 0.001). The CES-DC scores were 11.74 ± 6.11 in the patient group and 7.00 ± 3.97 in the control group (p < 0.001). And the PSQI scores were 2.58 ± 2.48 in the patient group, 1.15 ± 1.10 in the control group (p < 0.001). Also in the patient group, there was a positive correlation between participants’ ages and the PedsQL (p = 0.010; r = 0.256), the CES-DC (p = 0.000; r = 0.382), the PSQI (p = 0.000; r = 0.403) scores. The success parameters at school were significantly worse in the patient group (p = 0.05).

Conclusion

All our findings show us that the children with nocturnal enuresis were affected negatively because of their disease; especially when they grow up the scores get worse health, so we suggest that treatment must be started at suitable age according to guidelines.     

Hyperbaric oxygen for the treatment of nonhealing arterial insufficiency ulcers

There is limited data regarding hyperbaric oxygen's effectiveness in the treatment of nonhealing arterial insufficiency ulcers. This study was designed to analyze healing rates and amputation rates in patients who underwent adjunctive hyperbaric oxygen for a nonhealing arterial insufficiency ulcer. A retrospective chart review was completed on patients who underwent hyperbaric oxygen for arterial insufficiency ulcers that failed to heal despite standard treatment. Information collected included complete ulcer healing, amputation, and patient characteristics. There were 82 patients identified. A majority did not have diabetes (84.1%). The overall rate of healing was 43.9%. The overall major amputation rate was 17.1%. The amputation rate among those who healed was 0% compared to 42.4% among those not healed (p < 0.0001). Dialysis was predictive of major amputation (p = 0.03). Our findings suggest hyperbaric oxygen can play a role in management of arterial insufficiency ulcers that have failed standard treatment. The overwhelming majority of these patients did not have diabetes, which allows this study to be translated to patients with a primary arterial insufficiency ulcer. These results support the use of hyperbaric oxygen for select nonhealing arterial insufficiency ulcers that have failed standard therapy and the need for a prospective pilot study.     

The Effect of Bisphosphonates on Bone Mineral Density in Metastatic Prostate Cancer Patients Who Are Treated with Anti-Androgen Drugs and Radiotherapy

Objective

To evaluate the potential effect of bisphosphonates on bone mineral density (BMD) in patients who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer.

Materials and Methods

The data of 31 patients with metastatic prostate cancer who were treated with anti-androgen drugs and radiotherapy during a 1-year period were retrospectively reviewed. Patients were divided in 2 groups, in which 17 patients in group 1 were treated with zoledronic acid (4 mg/month, intravenous) and 14 patients in group 2 who did not receive zoledronic acid. BMD was measured before the treatment and at the end of the 1st year by dual energy X-ray absorptiometry. Statistical analyses were performed with the T test.

Results

Mean age of the patients was 71.42 ± 6.7(range 59-85) years. A significant increase was noted for pelvic bone, femoral neck, and lumbar vertebrae t scores when pretreatment and 1st year measurements were compared in group 1 (p < 0.05). In group 2 a significant decrease was noted for pelvic bone and femoral neck t scores at the end of the 1st year (p < 0.05). A significant increase was noted for pelvic bone and femoral neck follow-up in BMD values at the end of the 1st year compared to initial measurements in group 1. A significant decrease was noted for lumbar vertebrae follow-up in BMD values at the end of the 1st year when compared to initial values in group 2.

Conclusion

Zoledronic acid significantly increases BMD and delays unfavorable outcomes for bones in men who are treated with anti-androgen drugs and radiotherapy for metastatic prostate cancer.Key Words: Metastatic prostate cancer, Osteoporosis, Radiotherapy, Bisphosphonate therapy     

The phenotype of a flavin-containing monooyxgenase knockout mouse implicates the drug-metabolizing enzyme FMO1 as a novel regulator of energy balance

Flavin-containing monooxygenases (FMOs) of mammals are thought to be involved exclusively in the metabolism of foreign chemicals. Here, we report the unexpected finding that mice lacking Fmos 1, 2 and 4 exhibit a lean phenotype and, despite similar food intake, weigh less and store less triglyceride in white adipose tissue (WAT) than wild-type mice. This is a consequence of enhanced whole-body energy expenditure, due mostly to increased resting energy expenditure (REE). This is fuelled, in part, by increased fatty acid β-oxidation in skeletal muscle, which would contribute to depletion of lipid stores in WAT. The enhanced energy expenditure is attributed, in part, to an increased capacity for exercise. There is no evidence that the enhanced REE is due to increased adaptive thermogenesis; instead, our results are consistent with the operation in WAT of a futile energy cycle. In contrast to FMO2 and FMO4, FMO1 is highly expressed in metabolic tissues, including liver, kidney, WAT and BAT. This and other evidence implicates FMO1 as underlying the phenotype. The identification of a novel, previously unsuspected, role for FMO1 as a regulator of energy homeostasis establishes, for the first time, a role for a mammalian FMO in endogenous metabolism. Thus, FMO1 can no longer be considered to function exclusively as a xenobiotic-metabolizing enzyme. Consequently, chronic administration of drugs that are substrates for FMO1 would be expected to affect energy homeostasis, via competition for endogenous substrates, and, thus, have important implications for the general health of patients and their response to drug therapy.     

CYP2C19*17 increases clopidogrel‐mediated platelet inhibition but does not alter the pharmacokinetics of the active metabolite of clopidogrel

The aim of the present study was to determine the impact of CYP2C19*17 on the pharmacokinetics and pharmacodynamics of the active metabolite of clopidogrel and the pharmacokinetics of proguanil. Thus, we conducted an open‐label two‐phase cross‐over study in 31 healthy male volunteers (11 CYP2C19*1/*1, 11 CYP2C19*1/*17 and nine CYP2C19*17/*17). In Phase A, the pharmacokinetics of the derivatized active metabolite of clopidogrel (CAMD) and platelet function were determined after administration of a single oral dose of 600 mg clopidogrel (Plavix; Sanofi‐Avensis, Horsholm, Denmark). In Phase B, the pharmacokinetics of proguanil and its metabolites cycloguanil and 4‐chlorphenylbiguanide (4‐CPB) were determined in 29 of 31 subjects after a single oral dose of 200 mg proguanil given as the combination drug Malarone (GlaxoSmithKline Pharma, Brondby, Denmark). Significant correlations were found between the area under the time–concentration curve (AUC_0–∞) of CAMD and both the absolute ADP‐induced P2Y₁₂ receptor‐activated platelet aggregation (r = ?0.60, P = 0.0007) and the percentage inhibition of aggregation (r = 0.59, P = 0.0009). In addition, the CYP2C19*17/*17 and CYP2C19*1/*17 genotype groups had significantly higher percentage inhibition of platelet aggregation compared with the CYP2C19*1/*1 subjects (geometric mean percentage inhibition of 84%, 73% and 63%, respectively; P = 0.014). Neither the absolute ADP‐induced P2Y₁₂ receptor‐activated platelet aggregation, exposure to CAMD nor the pharmacokinetic parameters of proguanil, cycloguanil and 4‐CPB exhibited any significant differences among the genotype groups. In conclusion, carriers of CYP2C19*17 exhibit higher percentage inhibition of platelet aggregation, but do not have significantly lower absolute P2Y₁₂ receptor‐activated platelet aggregation or higher exposure to the active metabolite after a single oral administration of 600 mg clopidogrel.     

Niclosamide Modulates the Cellular and Humoral Immune Response in Balb/c Mice

Background: Niclosamide, a STAT3 inhibitor, is widely under investigation due to its anti-cancer properties. STAT3 also exhibits an exciting role in the immune responses. Objective: This study aimed to evaluate the impact of niclosamide on immune response of mice. Methods: Niclosamide was administered to balb/c mice. To evaluate cell-mediated immune response, a contact-hypersensitivity (CHS) test, cyclophosphamide-induced neutropenic assay, and carbon clearance test were performed, whereas a humoral immune response was evaluated by hemagglutination assay (HA) and mice lethality test. The concentration of TGF-β1 was determined by enzyme-linked immunosorbent assay (ELISA) on murine peritoneal macrophages. Results: In the CHS test, niclosamide caused a decrease in skin thickness, significantly exhibiting a decrease in inflammation. A highly significant decrease in overall leukocyte count (lymphocytes and neutrophils) was observed before and after cyclophosphamide injection as compared with the control group. However, only a highly significant decrease in the neutrophil percentage was observed. Niclosamide has decreased the phagocytic process immensely compared with the control. In the HA titer, niclosamide was found to reduce the antibodies' titer compared with the negative control group. In the mice lethality test, the treatment groups have shown an increase in the percentage of mortality. TGF-β1 elevated in peritoneal macrophages when treated with niclosamide, in a dose-dependent manner. Conclusion: Niclosamide exerts potent immunomodulatory effects by significantly suppressing cell-mediated and humoral immune responses and increasing the levels of TGF-β1 in mice. Niclosamide might be added as an adjuvant to immunosuppressive drugs for the treatment of autoimmune diseases.     

Evaluation of preoperative and postoperative serum interleukin-6, interleukin-8, tumor necrosis factor α and raftlin levels in patients with obstructive sleep apnea

Background

Raftlin is a large, major lipid raft protein of cell membranes. Raftlin levels have not been previously examined in patients with obstructive sleep apnea (OSA). Our study aimed to evaluate the changes in raftlin, interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor alpha (TNFα) values from the preoperative state to the third month postoperatively in patients undergoing expansion sphincter pharyngoplasty for OSA.

Methods

Of 60 patients, 10 patients had mild OSA (AHI 5–14), 10 moderate (AHI 15–29), 10 severe (AHI ≥ 30), and 30 with AHI < 5 formed a control group. Preoperatively and at 3 months post-operatively, IL-6, IL-8, TNFα, and raftlin values were measured.

Results

Preoperatively, mean raftlin levels were 914.4 ± 62.7 pg/mL for controls, 910.0 ± 42.5 pg/mL in mild, 1000.5 ± 63.3 pg/mL in moderate, and 1386.3 ± 101.4 pg/mL in severe groups, with moderate and severe groups significantly elevated compared to controls (p < 0.001). Preoperatively to 3 months post-operatively, raftlin levels decreased significantly in each OSA group (p < 0.05). Levels of IL-6, IL-8 and TNFα followed similar patterns at baseline and after surgical intervention.

Conclusions

Raftlin levels at the third postoperative month decreased significantly compared with preoperative levels in parallel with other markers of inflammation.

     

Toxicity of fungicides to Pisum sativum: a study of oxidative damage,growth suppression,cellular death and morpho-anatomical changes

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed. Fungicide applications in general caused a slow but gradual reduction in growth, symbiosis and yields of peas, which, however, varied appreciably among species and concentrations of the three fungicides. Of the three fungicides, carbendazim had the most lethal effect, in which it delayed seed germination and also diminished the overall pea growth. Carbendazim at 3000 μg kg⁻¹ maximally reduced the germination, SVI, size of roots and shoots and total dry matter accumulation in roots, shoots and whole plants distinctly by 40%, 84%, 72%, 73%, 68%, 75% and 73% (p ≤ 0.05), respectively. Hexaconazole at 120 μg kg⁻¹ significantly (p ≤ 0.05) declined total chlorophyll, carotenoids, grain yields, grain protein, root P and shoot N by 19%, 28%, 46%, 69%, 48% and 51%, respectively, over the control. The synthesis of stress biomarkers and oxidative stress were increased with increasing dosage rates of fungicides. Proline content in roots, shoots, leaves and grains, MDA, electrolyte leakage and H₂O₂ of plants grown in soil treated with 288 μg kg⁻¹ kitazin were increased significantly (p ≤ 0.05) by 73%, 52%, 41%, 24%, 59%, 40% and 27%, respectively, relative to the control. Antioxidant defence enzymes were greater in pea foliage. The SEM and CLSM images revealed an obvious alteration in root tips, enhanced cellular damage and cell death when plants were raised under fungicide stress. Also, morpho-anatomical variations in fungicide-treated foliage were visible in the SEM images. Overall, the present study suggests that a careful and secure strategy should be adopted before fungicides are chosen for enhancing pulse production in different agro-climatic regions.

Considering the fungicidal threat to the sustainable agro-environment, the toxicological impacts of three fungicides, namely kitazin, hexaconazole and carbendazim, on the biological, chemical and morpho-anatomical changes of peas were assessed.