Duygun Altıntaş Aykan

Takviye edici gıda (TEG) kullanımı, artan sağlık farkındalığına paralel olarak küresel düzeyde yaygınlaşmaktadır. Vitamin ve mineral gibi biyoaktif bileşenleri içeren TEG'ler, spesifik eksikliklerinin kompanzasyonu veya genel sağlık halinin optimizasyonu ile devamlılığı gibi potansiyel faydalar düşüncesiyle tüketilmekle birlikte, bilinçsiz ve kontrolsüz kullanım durumunda ciddi riskler barındırmaktadır. Bu risklerin tetikleyicileri arasında olası ilaç etkileşimleri, standardizasyon ve kalite kontrol yetersizlikleri, advers olay, toksisite ve kontaminasyon olasılığı bulunmaktadır. TEG'lerin farmakolojik bir tedavi modalitesi olmadığı, hastalıkların tedavi kalıbında öncelikli yer almadıkları ve konvansiyonel bir diyetin ikamesi olarak kabul edilemeyeceği hususu göz ardı edilmektedir. Akılcı ilaç kullanımı (AİK) prensiplerinin TEG kullanım pratiğine entegrasyonu, hasta güvenliğinin sürekliliği açısından gereklidir. Dolayısıyla, tüketicilerin TEG kullanımı noktasında algı ve bilgi düzeylerinin geliştirilmesi, rasyonel kullanım kararlarında hekimin mevcudiyeti, bilimsel kanıta dayalı güvenilir bilgi kaynaklarına erişimin temini, düzenleyici otoriteler tarafından etkin denetim ve farmakovijilans sistemlerinin işlevselliği kritik öneme sahiptir. Bu derlemenin amacı, TEG'lerin farklı ülkelerdeki düzenleme ve uygulamalarını karşılaştırmalı olarak ele almak, TEG'lerin potansiyel endikasyonlarını, olası yarar ve risklerini değerlendirmek ve bu ürünlerin AİK ilkeleri doğrultusunda nasıl konumlandırılması gerektiğine dair güncel literatür ışığında bir bakış açısı sunmaktır.

Objective: The most common adverse effects of statins are muscle disorders. This study investigated the effects of vitamin D, infliximab, and leflunomide on statin-induced rhabdomyopathy by evaluating myofibrillar contractions under electrical and mechanical stimulation. Materials and Methods: Twenty-four rats were induced rhabdomyopathy using atorvastatin (100 mg/kg/day for three weeks). The rats were then divided into four groups: Group 1 (n=6) received vitamin D (0.2 µg/kg), Group 2 (n=6) received infliximab (7 mg/kg), Group 3 (n=6) received leflunomide (10 mg/kg), and Group 4 (n=6) received saline as a control. In vitro organ bath experiments were performed using electrical and mechanical stimulations on the isolated extensor digitorum longus muscle to assess contraction responses. Blood and tissue samples were analyzed for creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), blood urea nitrogen (BUN), glutathione peroxidase (GPx), and malondialdehyde (MDA). Results: Group 1 demonstrated significant improvements in contractile responses (Twitch: Group 1 vs. Group 2, p=0.004; Group 1 vs. Group 3, p=0.025; Group 1 vs. Group 4, p<0.001. At 20 Hz: Group 1 vs. Group 2, p=0.018; Group 1 vs. Group 4, p=0.001; Group 3 vs. Group 4, p=0.015. At 80 Hz: Group 1 vs. Group 2, p=0.008; Group 1 vs. Group 3, p=0.0016; Group 1 vs. Group 4, p<0.001. At 100 Hz: Group 1 vs. Group 2, p=0.006; Group 1 vs. Group 3, p=0.015; Group 1 vs. Group 4, p<0.001). At 40–60 Hz and 120–140 Hz, Groups 1, 2, and 3 showed higher responses than Group 4 (p<0.05). Impulse conduction velocity in Group 1 was higher than in Group 4 (p=0.019). Group 1 exhibited significant differences in renal GPx (Group 1 vs. Group 3, p=0.023) and MDA (Group 1 vs. Group 2, p=0.001; Group 1 vs. Group 3, p=0.003). Additionally, Group 1 showed significant improvements in histopathologic evaluation compared to the control group (p<0.05). Conclusion: Vitamin D enhanced impulse conduction velocity and contraction response of striated muscle following electrical and mechanical stimulation in rhabdomyopathy. Monitoring vitamin D levels in dyslipidemic patients may serve as a predictive marker for adverse effects of statins. Providing these patients with vitamin D supplementation may improve statin intolerance.

Aim: Pitavastatin (Pita) is a member of the statin family, a well-known hypolipidemic agent, and some statin members are effective in treating pain. This study aimed to evaluate the antinociceptive effects of Pita by measuring nociception in rats with different doses and durations. Material and Methods: This study consisted of six groups including saline oral as a non-drug control, 1 mg/kg Pita single dose, 3 mg/kg Pita single dose, 1 mg/kg Pita for 14 days, 3 mg/kg Pita for 14 days, and 20 mg/kg diclofenac for 14 days. Thermal plantar and mechanical plantar tests were used to observe pain threshold changes. Correlations between Pita doses, durations, and behavioral pain responses were evaluated. The sciatic nerves were evaluated histopathologically. Results: Pita showed a significant antinociceptive effect in the dynamic plantar test at doses of 1 mg/kg for 14 days by increasing the mechanical threshold from 25.43±4.79 g to 32.28±2.27 g (p=0.041) and 3 mg/kg for 14 days by increasing the mechanical threshold from 27.41±2.36 g to 34.35±2.58 g (p=0.039). Also, Pita increased the thermal latency from 8.95±1.28 s to 11.71±1.49 s in the thermal plantar test at a single dose of 3 mg/kg (p=0.004). Although the antinociceptive effects of Pita were proven in dynamic plantar and thermal plantar tests, these findings did not reach a significant level at histopathological evaluation. Conclusion: These results suggest that Pita has an antinociceptive effect and when used in conjunction with the right dosage and timing, might be favored for the treatment of pain.

Aims: Less than 50% of patients treated for hypertension reach a target office systolic blood pressure (SBP). We aimed to evaluate the role of adiposity on antihypertensive drug responses in newly diagnosed hypertensive patients.Methods: Estimated glomerular filtration rates, body mass index (BMI), skinfold thickness (SFT), body surface areas and waist circumferences of 150 hypertensive patients naïve to treatment were measured. Treatment protocols were started as combination of angiotensin converting enzyme inhibitor (ACE‐I) plus calcium channel blocker (CCB), angiotensin receptor blocker plus CCB or ACE‐I plus diuretic. Pre‐treatment and change in blood pressure (ΔBP) after 4 weeks treatment were determined. Multiple linear regression analysis was used to find independent predictors of Δblood pressure changes, and multivariable binary logistic regression analysis to find independent predictors of target SBP < 140 mmHg at 4 weeks.Results: A total of 104 patients reached the target systolic pressure of P = .011, P = .006 and P = .016, respectively). Pretreatment SBP (r = 0.644), pretreatment diastolic blood pressure (DBP) (r = 0.188), subscapular SFT (r = −0.318), suprailiac SFT (r = −0.211) and ΔDBP (r = 0.433) were correlated with ΔSBP in correlation analysis. Pretreatment SBP (β = 0.644, 95% CI = 0.697–0.993, P < .001), subscapular SFT (β = −0.253, 95% CI = −0.886–−0.329, P < .001), pretreatment DBP (β = −0.380, 95% CI = −0.1001– −0.453, P = .001) and ΔDBP (β = 0.401, 95% CI = 0.377–0.796, P < .001) were independent predictors of ΔSBP in multivariable linear regression analysis. Subscapular SFT was an independent predictor of target SBP < 140 mmHg in multivariable logistic regression analysis (OR = 0.895, 95% CI = 0.832–0.963, P = .003).Conclusions: Subscapular SFT may be a valuable marker for prediction of response to antihypertensive drugs.

Purpose: Tadalafil, a long-acting phosphodiesterase-5 (PDE-5) inhibitor, is commonly used in the treatment of erectile dysfunction. This study investigates the contribution of tadalafil in cardiac function by measuring isometric and electrical contractions of myocardium in rats. Materials and Methods: Thirty rats were divided into five groups. Basal electrical contractions were recorded via electrocardiogram (ECG) for intervals PR (ms), QRS (ms), QT (ms), Tp (ms), Te (ms), pathological Q and heart beats/min. Then group 1 received saline for 7 days (control); group 2 received tadalafil 1 mg/kg; group 3 received tadalafil 10 mg/kg; group 4 received tadalafil 1 mg/kg for 7 days; group 5 received tadalafil 10 mg/kg for 7 days. After treatments, electrical contractions were re-performed to analyze the differences in ECG. For isometric contractions, hearts were connected to isometric power transducer to determine myocardial contractile forces (g), durations (ms) and frequencies (Hz). Serum samples were collected for cardiac creatine kinase (CK-MB) and cardiac troponin I via ELISA. Results: We found a significant decrease in CK-MB in Group 2 (395.56±124.38 pg/ml) and 3 (377.81±79.61 pg/ml), compared to Group 1 (575.32±83.54 pg/ml). The differences in cardiac contractile forces, contraction durations or frequencies were not statistically significant. Conclusion: Tadalafil did not exert obvious distruption on myocardial electrical or isometrical contractions. It is noteworthy that tadalafil 1 and 10 mg/kg reduced serum CK-MB. Shortening in QT and decrease in heart rate may have important implications on myocardial functions.

Introduction: We aimed to investigate the efficacy of local boric acid (BA) and teicoplanin in prosthetic vascular graft infection (PVGI) caused by methicillin-resistant Staphylococcus aureus (MRSA) in a rat model. Methodology: Fourty rats were divided into five groups. Group 1 received no treatments (control group); group 2 was uncontaminated polytetrafluoroethylene (PTFE) graft group; group 3 was untreated and the PTFE graft was contaminated with 2×107 CFU/mL MRSA; group 4 received local BA (8 mg/kg) and was contaminated with with 2×107 CFU/mL MRSA; group 5 received local BA (8 mg/kg) and intraperitoneal teikoplanin (10 mg/kg), and was contaminated with 2×107 CFU/mL MRSA; On the 3rd day, grafts and serums were removed for microbiological, histological and serological tests. Results: The amounts of culture growth in groups 4 and 5 were significantly lower compared to group 3 (p < 0.001). TNF-α was significantly higher in Group 3 than the other groups (p = 0.001). There was no significant difference between the groups in serum IL-1 levels (p = 0.138). Monocyte chemotactic protein-1 (MCP-1) was not significantly different between groups 3, 4, and 5, but it was significantly higher than groups 1 and 2 (p < 0.001). The severity of inflammation was significantly higher in group 3 than the other groups, and fibroblastic proliferation, granulation tissue and collagen synthesis were significantly lower (p < 0.05). Conclusions: Our study showed that local BA and combined teicoplanin treatment is effective in preventing PVGI.

Aim: Cisplatin (CP) is used to treat a variety of cancers as a chemotherapeutic agent. This drug has also severe side effects and its use exhibits serious toxicity in a number of organs, including kidney and heart. The aim of the present study was to evaluate the ultrastructural and inflammatory changes induced by CP treatment in rat cardiac tissue in a time-dependent manner. Material and Methods: Rats were randomly divided into three experimental groups; control (only saline), CP D2 (treated with CP 2.5 mg/kg/day for 2 days), and CP D7 (treated with CP 2.5 mg/kg/day for 7 days). Cardiac tissues were examined under an electron microscope. Inflammation markers including tumor necrosis factor-α (TNF-α) and interleukin 1β (IL-1β) were analyzed by immunohistochemistry. In addition, electrocardiography was performed to measure the electrical activity. Results: The ultrastructural analysis of the CP D7 group revealed that myofibrils were disrupted and disorganized, mitochondria degenerated, and interstitial edema developed. When compared to the control and CP D2 groups, there was a noticeable increase in the level of TNF-α and IL-1β expression in the CP D7 group according to immunohistochemistry results. Electrocardiography showed that RR interval was longer in CP D7 than CP D2 and control groups. Conclusion: CP for 7 days damaged the ultrastructural morphology in cardiac tissue. Therefore, these findings suggest that the potential therapeutic approaches to reduce mitochondrial damage and inflammation against toxicity caused by CP may provide for clinically significant prevention when using the drug for an extended period of time.

Gebelikte hipertansif bozukluklar, dünya çapında gebeliklerin en yaygın tıbbi komplikasyonlarındandır. Gebelik sırasında hipertansiyonu tedavi etme kararı, hem anne hem de fetüs için riskleri ve yararları göz önünde bulundurularak alınmalıdır. Hipertansiyon tedavisinin amacı maternal riski azaltmak olsa da, seçilen ajanlar fetüs için güvenli olmalıdır. Uzun vadeli prognoz, tahmini maternal risk ve beklenen fetal sonuçlar multidisipliner bir yönetim planı oluşturularak hasta ile paylaşılmalıdır. Bu çalışmada, gebelik sırasında hipertansiyon tedavisine ilişkin kılavuzlar, antihipertansif ilaçların gebelikte maruziyeti ile ilgili hayvan çalışmaları ve insan gebelik raporları incelenmiştir. Antihipertansif ilaçların gebelikte kullanımının güvenliliği ve oluşabilecek potansiyel teratojenik etkileri derlenmiştir.

Introduction: Little is known about the relationship between pain and hypertension (HT). This study aimed to analyze the effect of HT on pain sensitivity in patients with chronic musculoskeletal pain complaints. Methods: This analytical, cross-sectional study included 45 patients aged 29–75 years with HT. The control group comprised 44 normo/hypotensive patients aged 19–66 (P = 0.107). Education status, age, gender, height, weight, smoking, presence of diabetes mellitus, physical activity level, blood pressure measurement, anti-HT drug use, vital parameters, including heart rate, respiratory rate, and body temperature, were recorded for all participants. Results: The pain score was significantly higher in the HT group, with a mean of 72.1 ± 30.2 points (P = 0.008). Also, the HT group’s systolic blood pressure and pain score were significantly positively correlated (rho = 0.245, P = 0.02). The pulse rate was found to be significantly related to the pain score and pain threshold (P < 0.001); it was negatively correlated with algometer values (rho = –0.286, P = 0.015). Systolic pressure (P = 0.033) and BMI ( P < 0.001) were significantly different among the groups according to physical activity level. The Spearman correlation analysis showed a positive correlation of diastolic blood pressure with the body mass index (rho = 0.224, P = 0.036) and pain score (rho = 0.456, P < 0.001). Conclusion: The present study showed that the pain complaint increases as the blood pressure and weight increase. Also, the pain threshold decreases as the heart rate increases. The pain threshold was lower in women than in men, independent of tension.

Purpose: In this study, we applied platelet rich fibrin (PRF) and pure olive oil on the incision surfaces of rats. We aimed to examine whether PRF may be used safely to prevent peritoneal adhesions. Materials and Methods: Fourty rats were divided into 4 groups (n=8). Eight rats, not included in the study groups, were used to obtain PRF material. Group 1 had no surgical procedure, Group 2 was operated without medication, Group 3 was operated and received 1cc olive oil, Group 4 was operated and received 1 cc PRF. After 21 days, cecum areas were examined histopathologically. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1) and platelet-derived growth factor (PDGF) levels were measured in serum by ELISA. Results: The adhesion scores and severity of fibrosis in Group 3 and 4 were significantly lower than Group 2. Plasma TNF-α value was significantly higher in Group 2 than Group 4. Plasma PDGF value was significantly higher in Group 2 than Group 3 and 4. Discussion: PRF reduced intestinal adhesion by inhibiting the proliferation of fibroblasts and inflammatory cells, and promoting the proliferation of mesothelial cells. PRF has anti-inflammatory effect and prevented postop adhesions, based mainly on growth factors and cytokines in its content.