The effects of different vasovasostomy techniques on motility of vas deferens (vas motility following vasovasostomy).

PURPOSE: Vasovasostomy is used to correct vas deferens (VD) transections encountered during surgery or to reverse sterilization vasectomies. Achieving vasal patency is the primary goal and the success is assessed on various factors including VD patency, flow rates, and pregnancy rates. While preserving vas motility is not a major concern in surgical practice, it is worth noting that VD has peristaltic activity which plays crucial role during ejaculation. Any disruption in its motility could potentially lead to negative outcomes in the future. We conducted an experimental study to assess vas motility changes following vasovasostomy. METHODS: The study was approved by Gazi University, Animals Ethic Committee. Twenty-four rats were allocated to four groups. Left-sided VD was harvested in control group (Gr1). The rest of the animals were subjected to transection of VD. Gr2 and 3 underwent microscopic and macroscopic anastomosis, respectively, while Gr4 underwent vasal approximation. After 12 weeks, all left-sided VD were resected, electrical field stimulation (EFS) and exogenous drugs were applied to induce contractions. Statistical analyses were performed and p value < 0.05 was regarded as statistically significant. RESULTS: The first and second phases of EFS-induced contractile responses(CR) increased for Gr3 and decreased for Gr4 at submaximal and maximal frequencies. An increase only at maximal frequency for second phase EFS-induced CR was encountered for Gr2. α-ß-methylene-ATP-induced CR decreased for Gr3 and 4. Noradrenaline-induced CR increased for Gr2, and 3 and decreased for Gr4. CONCLUSION: The results suggest that vasovasostomy performed using a surgical technique that minimizes disruption or damage to VD may have a favorable impact on motility.

Evaluation of the Potentially Inappropriate Cardiovascular Medication Prescription in Elderly: A Nationwide Study in Turkey.

BACKGROUND: Elderly comprises a specific group due to possible alterations in the effects of drugs and comorbidities. We aimed to identify for the first time the characteristics and rates regarding the inappropriate prescriptions of cardiovascular system medications in the geriatric age group in Turkey. METHODS: Cardiovascular system medications prescribed electronically by family physicians to patients aged 65 and over, in the years 2015 and 2016, were obtained through Prescription Information System administered by the Ministry of Health. Evaluation of potentially inappropriate prescriptions was done according to the 'Beers Criteria 2015 update.' Prescription rates for each group were evaluated under sub-breakdowns for the specialty of family physicians, gender, age groups, and 'Nomenclature of Territorial Units for Statistics' regions. RESULTS: Approximately 65 million prescriptions were evaluated. The rate of potentially inappropriate cardiovascular medication prescribing was 0.33%. This raised to 11.56% when 'drugs to be used with caution' were included. It was observed that potentially inappropriate drugs have been prescribed more by specialist family physicians. The most frequently prescribed potentially inappropriate drugs were doxazosin in the diagnosis of hypertension and methyldopa regardless of indication. Diclofenac-warfarin was the most commonly prescribed concomitant drug use in the potentially clinically important drug-drug interactions group. The rate of potentially inappropriate drug prescribing was higher in males and in aged 80 years and older. CONCLUSIONS: This pharmacoepidemiological study draws attention to potentially inappropriate cardiovascular system drugs prescribed in primary care settings to the elderly. The rate of potentially inappropriate cardiovascular system drug prescribed was found to be very low in Turkey.

Profile of psychotropic agents used in autism spectrum disorder according to comorbidities in Turkey: A 4-year evaluation.

It is known that the use of psychotropic pharmaceuticals is common in comorbidities seen in autism spectrum disorder (ASD). We have very limited knowledge about which psychotropic drugs are prescribed when comorbidities are diagnosed in patients with ASD. It is aimed to determine the profile of psychotropic agents in patients diagnosed with ASD associated with comorbidities between the ages of 0-24 in Turkey over 4 years. Data belonging to ASD in Prescription Information System (PIS) was obtained from the 'Turkish Medicines and Medical Devices Agency'. A total of 34 066 prescriptions including 45 624 psychotropic drugs were analyzed. A total of psychotropic drugs prescribed for patients with ASD was 75.4%. The following psychotropic drugs were prescribed for the patients with ASD and its comorbidities; risperidone (28.6%), aripiprazole (13.7%), and valproic acid (11.3%) are the most preferred psychotropics. The percentage of pharmaceuticals containing psychotropic active substances in prescriptions with ASD and its comorbidities is 7.5%. This study is the first research in which psychotropics used in ASD were evaluated over a wide period and nationwide. Antipsychotics were most commonly prescribed with the diagnosis of ASD. In the presence of ASD and its comorbidities, risperidone was most frequently prescribed.

Assessment of quarter billion primary care prescriptions from a nationwide antimicrobial stewardship program.

We described the significance of systematic monitoring nationwide antimicrobial stewardship programs (ASPs) in primary care. All the prescriptions given by family physicians were recorded in Prescription Information System established by the Turkish Medicines and Medical Devices Agency of Ministry of Health. We calculated, for each prescription, "antibiotics amount" as number of boxes times number of items per box for medicines that belong to antiinfectives for systemic use (i.e., J01 block in the Anatomical Therapeutic Chemical Classification System). We compared the antibiotics amount before (2015) and after (2016) the extensive training programs for the family physicians. We included 266,389,209 prescriptions from state-operated family healthcare units (FHUs) between January 1, 2015 and December 31, 2016. These prescriptions were given by 26,313 individual family physicians in 22,518 FHUs for 50,713,181 individual patients. At least one antimicrobial was given in 37,024,232 (28.31%) prescriptions in 2015 and 36,154,684 (26.66%) prescriptions in 2016. The most common diagnosis was "acute upper respiratory infections (AURI)" (i.e., J00-J06 block in the 10th revision of the International Statistical Classification of Diseases and Related Health Problems) with 28.05%. The average antibiotics amount over prescriptions with AURI decreased in 79 out of 81 provinces, and overall rate of decrease in average antibiotics amount was 8.33%, where 28 and 53 provinces experienced decreases (range is between 28.63% and -3.05%) above and below this value, respectively. In the most successful province, the highest decrease in average amount of "other beta-lactam antibacterials" per prescription for AURI was 49.63% in January. Computational analyses on a big data set collected from a nationwide healthcare system brought a significant contribution in improving ASPs.

Evaluation of more than one billion outpatient prescriptions and eight-year trend showing a remarkable reduction in antibiotic prescription in Turkey: A success model of governmental interventions at national level.

PURPOSE: To present the antibiotic prescription trend between 2011-2018 at primary healthcare in Turkey in order to evaluate the effects of interventions at national level for providing rational prescription of antibiotics. METHODS: Electronic prescription data of the family physicians collected from January 1, 2011 to December 31, 2018 in 81 provinces of Turkey were recorded through the Prescription Information System and screened for the antimicrobial drugs. The interventions to promote rational antibiotic use during 2011-2018 in Turkey includes reminding the legislation to stop access of antibiotics without prescription, monitoring of antibiotic prescription behaviors of primary healthcare physicians, and education of healthcare workers and the public on the appropriate use of antibiotics. RESULTS: A total of 1 054 261 396 prescriptions for outpatients of all age groups were recorded during this period. Of the prescriptions written by family physcians, 34.94% were containing at least one antibiotic in 2011, which declined to 24.55% in 2018. Antibiotics constituted 13.99% of all the items in prescriptions in 2011 and 10.47% in 2018. Percentage of total antibiotic expenditure to the total drug expanditure decreased from 14.14% to 4.12% during 2011-2018. The most commonly prescribed antibiotics were amoxicillin and enzyme inhibitor combination, cefdinir, and cefuroxime during 2011-2018, with an increasing trend for prescription of first-line antibiotic, amoxicillin, in recent years. CONCLUSIONS: Governmental interventions at national level have contributed to reducing antibiotic prescription and increasing preference of first-line antibiotics at primary healthcare level in Turkey over a course of 8 years. Turkey's model of governmental interventions may set an example for other countries with high consumption of antibiotics, and contribute to the actions against antimicrobial resistance worldwide.

Knowledge, opinions and attitudes of primary care physicians about generic drugs: a cross-sectional study.

BACKGROUND: Generic drug (GD) use is affected by many factors, including physicians' approach. OBJECTIVE: This study aimed to investigate the knowledge, opinions and attitudes of primary care physicians (PCPs) about GDs and potentially associated factors. METHODS: An adequately representative sample (n = 354) of PCPs was determined via stratified and simple random sample selection method in this descriptive, cross-sectional study. The research data were collected through a face-to-face 40-item survey, where the knowledge, opinions and attitudes about GDs were questioned. The prescribing percentage of GDs overall was also examined. RESULTS: The survey was completed by 305 PCPs (mean age: 49.2 ± 7.9 years; 57.4% male). The rate of correct responses about GDs was 67.6% for basic knowledge and 46.6% for the development process. The percentages of PCPs who declared that GDs were 'less efficacious', 'of lower quality' and 'less safe' than original drugs were 65.2%, 53.4% and 35.4%, respectively. More than half (60.3%) of the PCPs declared not to pay attention to whether the drug is generic while prescribing. It was observed that, as the knowledge level of the physicians increased, negative opinions and prescribing attitudes regarding the effectiveness, quality and safety of the GDs decreased. The rate of GD prescribing (51.6%) in Izmir was lower than the rest of the country (54.6%; P < 0.001). CONCLUSION: This study shows that the knowledge of PCPs about GDs is generally inadequate, which reflects negatively on their opinions and attitudes regarding the use of GDs. Educational activities can help establish awareness that GDs can be used without doubt of their effectiveness, quality and safety.

Effects of epoxygenases on the nonadrenergic noncholinergic relaxant responses induced by electrical field stimulation in rabbit corpus cavernosum.

We aimed to investigate the effects of epoxygenases on electrical field stimulation (EFS)-mediated nitric oxide (NO)-dependent and NO-independent nonadrenergic noncholinergic (NANC) relaxations in isolated rabbit corpus cavernosum. The tissues of 20 male adult albino rabbits (2.5-3 kg) were suspended in organ baths containing aerated Krebs solution, and isometric contractions were recorded. EFS-mediated NANC relaxations were obtained on phenylephrin (3 × 10-5  M)-contracted tissues in the presence of guanethidine (10-6  M) and atropine (10-6  M). Miconazole (10-9 -10-4  M), 17-octadecynoic acid (ODYA) (10-10 -10-5  M), 14,15-epoxyeicosatrienoic acid (EET) (10-11 -10-8  M), 11,12-EET (10-12 -3 × 10-8  M) and 20-hydroxyeicosatetraenoic acid (HETE) (10-11 -3 × 10-8  M) were added cumulatively (n = 5-7 for each set of experiments). For NO-independent relaxations, Nω -nitro-l-arginine methyl ester (l-NAME) (10-4  M) was added before a group of experiments. Depending on the concentration, miconazole, 17-ODYA, 14,15-EET, 11,12-EET, and 20-HETE significantly enhanced both NO-dependent and NO-independent EFS-mediated relaxations (p < 0.05). Epoxygenases showed similar effect on NO-dependent and NO-independent relaxant responses except 20-HETE which caused significantly more enhanced relaxation on NO-dependent responses (p < 0.05). No drug caused a significant relaxation response on tissues contracted with phenylephrine. Epoxygenases contribute to EFS-mediated NO-dependent and NO-independent NANC relaxations by presynaptic mechanisms, offering a new treatment alternative for erectile dysfunction which needs to be explored in further in vivo, molecular and clinical studies.

Relative risk of tuberculosis in patients with rheumatic diseases managed with anti-tumour necrosis factor-alpha therapy: A nationwide cohort study.

WHAT IS KNOWN AND OBJECTIVE: Anti-tumour necrosis factor-alpha (anti-TNF-α) therapy is known to raise the risk of granulomatous infections, leading to development of risk management strategies at national or global level. This study aimed to determine the relative risk (RR) of tuberculosis (TB) due to anti-TNF-α usage in patients with rheumatologic diseases (RDs) in a nationwide basis. METHOD: This retrospective cohort study included patients with rheumatoid arthritis (RA), ankylosing spondylitis, juvenile idiopathic arthritis or psoriatic arthritis (PsA) that treated with or without anti-TNF-α agents, as registered in the national prescription information system between years 2013 and 2015. Two-year RR of TB after anti-TNF-α therapy initiation was calculated in this RD population, including main subgroups. RESULTS AND DISCUSSION: The study cohort included 413 500 RD patients, where anti-TNF-α(+) arm (n = 2117) had mean age of 41.9 ± 13.4 years and male distribution of 54.3%. Four patients among anti-TNF-α users developed TB compared to 128 patients in anti-TNF-α-naïve group (189 vs 31 cases per 100 000 patients, respectively), yielding a 2-year RR of 6.07 (95% CI, 2.25-16.42) with an attributable risk of 0.16%. These RRs (95% CI), which were particularly pronounced, were 5.39 (1.69-7.17) in men, 6.12 (2.26-16.55) in adults, and 5.70 (1.41-23.08) in RA and 13.46 (1.58-114.40) in PsA patients. There was no difference between the anti-TNF-α users who developed and undeveloped TB regarding drug utilization characteristics, except significantly less immunosuppressive drug exposure in TB patients. WHAT IS NEW AND CONCLUSION: This study is the first prescription-based nationwide study to suggest an elevated RR of TB in a comparably younger population with a broad spectrum of RDs managed with any approved anti-TNF-α drug in Turkey.

Synthesis and photodegradation studies of analogues of muscle relaxant 1,4-dihydropyridine compounds.

This paper describes the synthesis of 1,4-dihydropyridine compounds (DHPs) endowed with good muscle relaxant activity and stability to light. Six new condensed DHPs were synthesized by the microwave irradiation method. A long-chain ester moiety [2-(methacryloyloxy)ethyl] and various substituents on the phenyl ring were demonstrated to affect the muscle relaxant activity occurring in isolated rabbit gastric fundus smooth muscle strips. Forced photodegradation conditions were applied to the molecules according to the ICH rules. The degradation profile of the drugs was monitored by spectrophotometry coupled with the multivariate curve resolution technique. Formation of the oxidized pyridine derivative was observed for all the studied DHPs, except for one compound, which showed very fast degradation and formation of a second photo-product. Pharmacological tests on the molecules showed a good muscle relaxing effect, with a mechanism similar to that of nifedipine, however, proving to be more stable to light.

Rational use of medicine in dentistry: do dentists prescribe antibiotics in appropriate indications?

PURPOSE: There are concerns regarding appropriate use of antibiotics in dentistry practice. Data on dental antibiotic prescribing patterns by dentists is relatively limited. This nationwide study aimed to examine dentists' antibiotic prescriptions in a diagnosis-based manner in Turkey. METHODS: This retrospective study on utilization of systemic antibiotics for dental problems was based on the national health data of the dentists obtained from Prescription Information System between January 2013 and August 2015. Only those prescriptions containing single diagnosis and at least one systemic antibiotic were included in the study. Antibiotic prescribing was compared by diagnoses and expertise of dentists. RESULTS: A total of 9,293,410 antibiotics were detected in 9,214,956 prescriptions that contained "single diagnosis and at least one antibiotic." The number of antibiotics per prescription was 1.01. "Periapical abscess without sinus" (28.1%), "dental examination" (20.7%), and "dental caries" (16.2%) were the three most common indications in which antibiotics were prescribed by dentists. While only 3.4% of antibiotics were prescribed upon the single and appropriate "cellulitis and abscess of mouth" diagnosis, the remaining 96.6% was prescribed for irrational/uncertain indications. Consistent in all diagnoses, "amoxicillin + enzyme inhibitor" (58.6%) was the mainly prescribed antibiotic. Analysis of the most preferred "amoxicillin + enzyme inhibitor" prescriptions by expertise of dentists showed significantly much higher prescription rates among Group A specialists and Group B specialists (67.0 and 67.8%, respectively) than those in unidentified dental practitioners (58.2%, p < 0.0001). CONCLUSIONS: This study showed that dentists prescribed antibiotics in an arbitrary and mostly unnecessary manner. In general, their antibiotic choices for examined diagnoses could be regarded as irrational. These results indicate the urgent need for improvement of rational antibiotic prescribing habits of dentists.

The effects of hydrogen sulfide on electrical field stimulation-induced neurogenic contractile responses in isolated rabbit lower esophageal sphincter: Contribution of nitrergic and non-adrenergic non-cholinergic transmission.

BACKGROUND: Hydrogen sulfide (H2S) is a gaseous signaling molecule that, similar to nitric oxide (NO), plays an important role as an inhibitor neurotransmitter in the digestive tract. This study aimed to investigate the effect of H2S and to identify neurogenic contraction responses dependent on the electrical field stimulation (EFS) in the isolated lower esophageal sphincters of rabbits. METHODS: An isolated lower esophageal sphincter was placed in an organ bath system and mechanical responses were recorded using a force transducer. The nerve-evoked contractile responses were obtained by EFS. The contractile responses were obtained as biphasic "on" and "off" phases seen at the beginning and end of EFS, respectively. RESULTS: Sodium hydrogen sulfide (NaHS) reduced the EFS-mediated "off" phase and the EFS-mediated non-adrenergic non-cholinergic (NANC) "off" phase. NaHS reduced the EFS-mediated "on" phase as well. l-Cysteine ​​reduced the EFS-mediated "off" phase and the EFS-mediated NANC "off" phase. l-Propargylglycine (PAG) did not affect the EFS-mediated "off" phase or the EFS-mediated NANC "off" phase. NaHS, l-cysteine, and PAG reduced the EFS-mediated, NO-independent "off" phase. The effect of NaHS in all of the experiments returned in time. Also, NaHS caused significant relaxation of 80-mM KCl-Krebs solution induced-contractions, while l-cysteine ​​and PAG did not cause a significant relaxation. CONCLUSION: These findings suggest that H2S has an inhibitory effect on the lower esophageal sphincter muscle. While the effect of H2S on EFS-mediated responses disappeared in time, the effect of H2S sustained the KCl-Krebs solution-induced contractions. This shows that H2S may have an effect on neurotransmission at the nerve terminal.

Effects of chronic l-DOPA administration on neurogenic and endothelium-dependent relaxation responses in rabbit corpus cavernosum.

BACKGROUND: Dopamine is a crucial central neurotransmitter that plays a fundamental role in the autonomic and somatic components of penile reflexes in animals and humans. Similar to the erectile responses of dopamine, systemic administration of l-DOPA induces yawning and penile erection in some species. The possible effects of l-DOPA on nitric oxide (NO)-dependent and -independent non-adrenergic non-cholinergic (NANC) relaxation responses mediated by electrical field stimulation (EFS) and endothelium-dependent relaxation were investigated in this study. METHODS: Thirty-two adult albino male rabbits, in two- and four-week-treatment groups, were divided into three subgroups: control group (saline-injected) (n=4), 3mg/kg/day (low dose) l-DOPA-injected groups (n=6) and 12mg/kg/day (high dose) l-DOPA-injected groups (n=6). After the intraperitoneal injection treatments, the corpus cavernosum tissues were placed in organ bath chambers. The EFS-mediated responses, and the concentration-response curve to carbachol, sodium nitroprusside (SNP), sildenafil were assessed. RESULTS: The two-week treatment with high-dose l-DOPA decreased the NO-dependent NANC relaxation responses, while there was no change in the low-dose two- and four-week treatment groups. The NO-independent NANC relaxation responses in the two-week groups decreased, and the responses in the four-week groups were unchanged when compared to the controls. The relaxation responses to carbachol showed no differences among all groups except for the high-dose four-week l-DOPA group. The relaxation responses of SNP and sildenafil were increased in all of the treatment groups when compared to the controls. CONCLUSIONS: The observed increases in SNP- and sildenafil-induced responses, along with the decreased EFS-mediated responses, suggest increased sensitivity in the NO-signalling pathway following l-DOPA administration.

Microwave-assisted synthesis and myorelaxant activity of 9-indolyl-1,8-acridinedione derivatives.

In this study a microwave-assisted method was applied for the synthesis of novel 9-(substituted indolyl)-3,4,6,7-tetrahydroacridine-1,8-(2H,5H,9H,10H)-dione derivatives. The structures of the compounds were confirmed by spectral methods including X-ray studies and elemental analysis. The Emax and pD2 values of the compounds and pinacidil were determined on noradrenaline precontracted tissues of isolated strips of rabbit gastric fundus smooth muscle. The obtained results indicated that some compounds and pinacidil produced concentration-dependent relaxation on the strips. The efficacy of compound 9 was higher than pinacidil. Docking studies were carried out to understand the interactions of the compounds with the active site of potassium channel. Methyl substituents on the acridine backbone and bromine atom on the indole ring led to more active compounds.