Delivery of salmon calcitonin using a microneedle patch

Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL min). T_max (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.     

Surgical results and prognosis of patients with primary bronchogenic carcinoma aged less than 36 years

BACKGROUND AND OBJECTIVE: This study reports on the demographic features, clinico-pathological results and prognoses of patients aged less than 36 years diagnosed with non-small cell lung cancer (NSCLC). METHODS: This is an observational study of patients with primary NSCLC who had a surgical procedure at a tertiary thoracic surgery centre in Turkey. Data collected were age, gender, history of smoking, symptoms, postoperative histopathological diagnosis, stage, surgical procedure and survival. RESULTS: Of the 31 patients in the study, 27 were male (87%) and the median age was 32 years (10-35 years). Nineteen patients were smokers (61.2%). The most common presenting symptom was cough (n = 23, 67.7%). Histopathological diagnosis was squamous cell carcinoma (SCC, n = 17), adenocarcinoma (n = 12), lymphoepithelioma-like carcinoma (n = 1) and undifferentiated carcinoma (n = 1). Staging of the 17 patients with SCC (58.8%) was stage I and II (n = 10, 58%), and stage III (n = 7, 41%). Staging of the 13 patients with adenocarcinoma was stage IV (n = 2, 16%) and stage III patients (n = 8, 66%). Follow-up data were available on 22 patients (71%) and showed a median survival of 17.2 months. Two and 5-year survival rates were 54.5% and 45.5%, respectively. CONCLUSIONS: SCC comprised a relatively high proportion of NSCLC in these younger patients. Aggressive multimodality treatment may achieve satisfactory 2- and 5-year survival rates in young patients with NSCLC who usually present with advanced disease.     

The relationship of chronic angiotensin converting enzyme inhibitor use and coronary collateral vessel development

BACKGROUND: Angiotensin II induces various growth factors such as vascular endothelial growth factor, platelet-derived growth factor, and fibroblast growth factor, and recent studies suggest that the expression of these growth factors promotes collateral growth. We hypothesized that the blockage of angiotensin II production by ACE inhibitors might interfere with collateral development in patients with coronary occlusion. METHODS: The study group consisted of 187 patients (114 males, mean ages, 62 +/- 11 years) who had chronic (> 1 month) coronary occlusion (TIMI flow grade < or = 1) in one of 3 epicardial coronary arteries. Collaterals were graded using the Rentrop classification, and the patients were divided into 2 groups according to having good (grade 2 and 3) or poor (grade 0 and 1) collaterals (n = 127 and 60, respectively). Clinical and angiographic characteristics were compared in the 2 groups. RESULTS: ACE inhibitor use (52% versus 35%, P = 0.04) and the prevalence of diabetes mellitus (DM) (43% versus 27%, P = 0.02) was higher in patients with poor collaterals. Patients with poor collaterals had a higher frequency of circumflex artery (Cx) occlusion, worse wall motion, and lower ejection fraction. In multivariate analysis, ACE inhibitor use (OR: 2.4; 95% CI = 1.23-4.68, P = 0.01) and the occlusion of Cx (OR: 3.3, 95% CI; 1.33-8.12, P = 0.01) were found to be independent predictors for poor collateral development, whereas there was a trend for DM as a predictor for poor collaterals (OR: 1.9, 95% CI = 0.97-3.8, P = 0.06). CONCLUSION: The findings suggest that ACE inhibitor therapy may contribute to poor collateral development in patients with coronary occlusion.     

Effect of prenatal exposure to an anti-inflammatory drug on neuron number in cornu ammonis and dentate gyrus of the rat hippocampus: a stereological study

Prenatal exposed to an anti-inflammatory drug is a major problem for the developing central nervous system. It is not well known the effect of prenatal exposed to a non-steroidal anti-inflammatory drug on the hippocampus. Total neuron number in one side of the cornu ammonis (CA) and gyrus dentatus (GD) of the hippocampal formation in control and drug-treated (diclofenac sodium, DS) groups of male rats was estimated using the optical fractionator technique. Each main group has also two subgroups that are 4 weeks old (4W-old) and 20 weeks old (20W-old). In CA, no significant difference between 4W-old DS-treated and their control was found, but a significant difference was observed between 20W-old DS-treated and their controls. A decreasing of neuron number was 12% for 20W-old DS-treated group. In GD, a decreasing of the granule cell number in 4W-old of DS-treated group was seen but an increasing of granule cell number was found in the 20W-old drug-treated rats in comparison to its control group, 7% and 9%, respectively. Although an increasing of neuron number in CA at the control group was seen with age, from 4th week to 20th week (10%), age-dependent substantial granule cell decline (17%) was observed in GD. No age effect on the total cell numbers of CA and GD of the drug-treated groups was seen in comparison to 4W-old week and 20W-old. A pronounced neuron loss observed in the drug-treated group may be attributed to the neurotoxicity of diclofenac sodium (DS) on the developing hippocampal formation. Age-dependent neuron increase in the CA of 20W-old and neuron decline in GD of 20W-old control groups may be a result of a dual effect of saline injection during the fetal life, since these animals were exposed to a stress of 15-day-period of saline injection, prenatal stress. The reason of no age effect on CA and GD cell number in the drug-treated groups may be attributed to the depletion of the progenitor cells due to neurotoxicity of DS in the fetal life of these animals.     

Clinical predictors of therapeutic response to clozapine in a sample of Turkish patients with treatment-resistant schizophrenia

BACKGROUND: Several lines of evidence suggest that clozapine is more effective than both first- and second-generation antipsychotic drugs in treatment-resistant schizophrenia (TRS). However, clinicians appear to be hesitant to prescribe this drug. It would therefore be extremely valuable if predictors of response to clozapine could be identified. The aim of this study was to evaluate the predictive factors of clinical responses to clozapine in a group of Turkish patients with TRS. METHODS: This was a 16-week uncontrolled open study carried out among 97 TRS patients (80 males and 17 females; DSM-IV diagnosis). All patients fulfilled the criteria for refractory schizophrenia according to the UK guidelines for the National Institute of Clinical Excellence (NICE). After all previous antipsychotic medications had run their course, the patients were started on clozapine according to a standardized titration and dosage schedule. Psychopathology was evaluated before the initiation of clozapine therapy and once every 4 weeks using the Brief Psychiatric Rating Scale (BPRS), the Scale for the Assessment for Positive Symptoms, and the Scale for the Assessment of Negative Symptoms. RESULTS: Of the TRS patients on clozapine, 55.7% achieved a clinical response, defined as at least a 20% decrease in BPRS. We observed a favorable effect of clozapine on both positive and negative symptoms. Logistic regression analysis showed that a good clozapine response was more likely when schizophrenia began at a later age, when negative symptoms were severe, and when patients had an early response at 4 weeks. CONCLUSION: A combination of demographic, baseline clinical, and acute treatment response variables may accurately predict response to clozapine in TRS. Priority should be given to initiating clozapine at the earliest phase of TRS, especially for patients with evident negative symptoms.     

The effect of budesonide mouthwash on oral chronic graft versus host disease

Oral chronic graft versus host disease (cGVHD) is common and a major cause of morbidity and loss of quality of life in long term survivors. Cyclosporine with prednisone remains the first line therapy for oral manifestations of cGVHD. However, even with routine administration of systemic agents, many patients with oral manifestations of cGVHD do not have resolution of their disease and may benefit from incorporation of local therapy. Budesonide is a highly potent steroid which has minimal systemic side effects and being used for oral cGVHD. We designed a retrospective study to compare treatment results of patients with oral cGVHD who received topical budesonide in addition to systemic therapy that consists of combined prednisone and cyclosporine (Group A, n = 12), with the treatment results of patients who were administered the same systemic therapy alone (Group B, n = 11) to determine whether budesonide mouthwash had any advantage on response rates. Three mg topical budesonide/10 ml saline was used 3-4 times a day for up to 6 months in group A. Diagnosis, clinical staging, and treatment response scoring for cGVHD were performed according to National Institutes of Health (NIH) consensus criteria. At the baseline examination, there were no statistically significant differences in terms of median oral cGVHD examination scores between two groups. After treatment, there was statistically significant decrease in median oral cGVHD examination scores compared to baseline (P < 0.001 and 0.021), and significant differences were found between two groups (P < 0.032). Overall response rate was 83% and 36% for group A and B, respectively (P = 0.036). However, no statistically significant differences were found between median pain scores of two groups before and after treatment (P = 0.740 and P = 0.091). No major systemic side effects and oral candidiasis were observed in two groups of patients. We concluded that topical budesonide might be added to systemic therapy to obtain better response rates in patients with oral cGHVD.     

Cognitive dysfunction in beta-thalassemia minor

Beta-thalassemia minor is a common, hereditary, and mostly symptomless disease. Previous studies have shown that lower hemoglobin values are associated with poorer cognitive functions. We aimed to evaluate the cognitive function in patients with beta-thalassemia minor. Thirty-two male subjects with beta-thalassemia minor and 32 sex-, age-, and education status-matched healthy subjects were enrolled in the study. Blood tests and P300 potentials were carried out. P300 potential latency in all patients was significantly longer than those in the control group (337.63+/-34.89 msec and 310.66+/-14.30 msec, respectively; t 4.046, P<0.001). The amplitudes of P300 in patient group were significantly lower than those in the control group (5.19+/-3.59 microV and 9.81+/-3.33 microV, respectively; t 5.349, P<0.001). In this study, we have found that P300 potentials are adversely affected for cognitive functions in patients with beta-thalassemia minor.     

Value of tissue Doppler myocardial velocities of tricuspid lateral annulus for the diagnosis of right heart failure in patients with COPD

OBJECTIVE: Aim of this study was to investigate the value of systolic indices of tricuspid valve annular motion measured by tissue Doppler imaging for the diagnosis right ventricular failure in patients with chronic obstructive pulmonary disease (COPD). METHODS: Patients with COPD with right heart failure symptoms and/or right ventricular dilatation were enrolled for the study. The control group consisted of age and sex matched patients referred to the echocardiography laboratory who had normal echocardiographic examination. Tricuspid valve annulus peak systolic velocity and myocardial acceleration during isovolumic contraction were recorded by tissue Doppler imaging. RESULTS: IVA and Sa wave velocities were found to be significantly decreased in patients with right ventricular failure. For the prediction of right heart failure IVA <3.8 m/sec2 had 91% sensitivity, 80% specificity, 90% positive predictive value (PPV), and 82% negative predictive value (NPV) and Sa wave velocity <9.2 cm/sec had 80% sensitivity, 62% specificity, 75% PPV, and 68% NPV. CONCLUSION: Tricuspid valve annular velocities measured by tissue Doppler imaging especially IVA, offer potential diagnostic value for the diagnosis of right heart failure in patients with COPD.