A kynurenine pathway enzyme aminocarboxymuconate-semialdehyde decarboxylase may be involved in treatment-resistant depression, and baseline inflammation status of patients predicts treatment response: a pilot study.

The kynurenine pathway (KP) and inflammation are substantial in depression pathogenesis. Although there is a crosstalk between the KP, inflammation, and neurotrophic factors, few studies examine these topics together. Novel medications may be developed by clarifying dysregulations related to inflammation, KP, and neurotrophic factors in treatment-resistant depression (TRD). We aimed to evaluate the serum levels of KP metabolites, proinflammatory biomarkers, and brain-derived neurotrophic factor (BDNF) in healthy controls (HC) and the patients with TRD whose followed up with three different treatments. Moreover, the effect of electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) on biomarkers was investigated. Study groups comprised a total of 30 unipolar TRD patients consisting of three separate patient groups (ECT = 8, rTMS = 10, pharmacotherapy = 12), and 9 HC. The decision to administer only pharmacotherapy or ECT/rTMS besides pharmacotherapy was given independently of this research by psychiatrists. Blood samples and symptom scores were obtained three times for patients. At baseline, quinolinic acid (QUIN) was higher in the patients with TRD compared to HC, whereas picolinic acid (PIC), PIC/QUIN, and PIC/3-hydroxykynurenine were lower. Baseline interleukin-6 (IL-6), and high-sensitivity C-reactive protein (hsCRP) were higher in nonresponders and non-remitters. ECT had an acute effect on cytokines. In the rTMS group, tumor necrosis factor-α (TNF-α) decreased in time. PIC, QUIN, and aminocarboxymuconate-semialdehyde decarboxylase (ACMSD) enzyme may play a role in TRD pathogenesis, and have diagnostic potential. rTMS and ECT have modulatory effects on low-grade inflammation seen in TRD. Baseline inflammation severity is predictive in terms of response and remission in depression.

Effective chronic low back pain and knee pain treatment with acupuncture in geriatric patients.

BACKGROUND: The most common disease of the older age group in Turkey is degenerative articular disease and pain associated with the disease. Analgesics and physical therapy are preferred treatment for geriatric chronic pain but suffering from multiple medical and nutritional problems in old ages can limit treatment options with analgesics due to an increased risk of adverse effects and drug interactions. OBJECTIVES: We aim to show the effect of acupuncture on back-pain and knee-pain treatment of elderly people. METHODS: The study includes 34 patients, 24 female and 8 male. The mean age was 69.0417 ± 8.95 years for females and 73.12 ± 8.95.24 years for males. Every two days for a total of 10 sessions acupuncture treatment to Yintang, Ht 7 (Shenmen), LI 4 (Hegu), Ki 3 (Taixi) and Ki 6 were found to significantly reduce pain scores of patients. RESULTS: Mean back pain scores (8.8696 ± 1.546) and mean knee pain scores (9.1304 ± 1.4239) of patients were reduced significantly to 2.1739 ± 1.466 and 1.455 ± 0.7; p< 0.001 respectively after the acupuncture treatment. CONCLUSION: These are important results as they give rationale to use acupuncture treatment widely in chronic low back pain and knee pain in the geriatric group of patients to reduce the side effects of polypharmacy in elderly.

Acupuncture for neuropathic pain due to bortezomib in a patient with multiple myeloma.

Multiple myeloma (MM) is characterised by an increase in plasma cells, particularly in the bone marrow but also in other organs and systems, and with the abnormal production of immunoglobulin. Bortezomib, a current treatment option, inhibits angiogenesis by proteasome inhibition and is known to be effective in the treatment of MM. Peripheral neuropathy (PN) is a common dose-related side effect of bortezomib in patients with MM. We describe a case of PN due to bortezomib treatment which responded dramatically to acupuncture treatment, enabling his bortezomib treatment to continue. The patient was a 74-year-old man with pain, numbness, tingling and weakness in his hands and feet after 22 days of bortezomib treatment given by the haematology clinic. His neuropathic pain score was 8/10. There were no autonomic symptoms. Electroneurophysiological testing confirmed sensorimotor PN. Acupuncture treatment was planned as his neuropathic pain continued. Acupuncture was administered bilaterally to ST36, SP6 and LI4 15 times (every other day in the first five sessions and then twice a week). The numbness, tingling and pain symptoms substantially decreased after the first two treatments. After the 15th session acupuncture treatment was continued once a month. At the end of the sixth month the neuropathic pain assessment score was 0/10. There was no side effect of acupuncture treatment. Acupuncture seems promising as a complementary medical treatment for neuropathic pain from bortezomib-induced PN. Clinical studies involving more cases and electrophysiological studies are necessary to investigate the effectiveness of acupuncture.

The impact of acupuncture treatment on nitric oxide (NO) in migraine patients.

The purpose of this study is to contribute to efforts to understand the pathophysiology of migraine and create an alternative perspective for prophylaxis and treatment of migraine attacks. Acupuncture treatment was applied to the 22 volunteer migraine patients. The acupuncture treatment consists of 5 sessions with 2 sessions per week. Blood samples have been collected before performing acupuncture, after the 1st session and after the 5th session of the acupuncture. And for the control group blood samples were collected only once. In our study the mean serum NO levels in healthy people were (3.58 ± 0.53) while patients with migraine group were (5.55 ± 0.70) respectively. Serum NO levels were 55% higher in migraine group compared to the control group. The NO concentration also decreased after 5th session (30%) (p < 0.05). After the 1st sessions NO level decreased 4.86% in the migraine group. After the 5th session NO level decreased 30.63% in the migraine group. After the 5th session NO level decreased 27.08% compared to 1st session in the migraine group. After the 1st session of acupuncture treatment, level of NO in migraine group were 4.86% and it is reduced but statistically not significant. After the 5th acupuncture treatment serum NO levels were reduced to (3.85 ± 0.62) 30.63% in migraine group and were statistically lower (p < 0.05). After the 5th session NO level decreased 27.08% compared to 1st session in the migraine group. In this study, acupuncture treatment is appeared to be effective by lowering the levels of serum NO and acupuncture has cumulative effects. Although there are earlier studies showing the effect of NO in migraine, this has been the 1st study in this field, which shows the effect of acupuncture on NO in migraine patients.

The effect of acupuncture on high blood pressure of patients using antihypertensive drugs.

Blood pressure control is an important component of cardiovascular disease prevention. Despite the advances in the treatment of hypertension; effective management remains poor. The combined use of multiple drug strategies fail to regulate blood pressure and chronic use of those agents cause severe side-effects. New strategies are required to control high blood pressure. We aim in our study to research the effects of acupuncture treatment on blood pressure of hypertensive patients who have already been exposed to antihypertensive drug therapy for at least 24 months. Each patient was using 1-3 antihypertensive drug of a heterogeneous pharmacological group ranging from ACE inhibitors, diuretics, and beta blockers and the most common complaint of those patients were fatigue, dizziness, weakness, headache and joint pain, sleeping problems, cold hands and feet, edema, depression. We did not alter patients' diet (salt intake), physical activity or use of antihypertensive drugs. The study includes 24 male and 10 female patients. Ki 3 (Taixi), Liv 3 (Taichong), Sp 9 (Yinlingquan), L.I. 4 (Hegu), Ht 7 (Shenmen), St 36 (Zusanli), Sp 6 (Sanyinjiao), Ki 7 (Fulio), Lu 9 acupuncture points were needled. After being treated with acupuncture for one month in every two days for a total of 15 sessions, we found significant reductions (p ? 001) in both systolic (from 163.14 +/- 19.33 to 129.49 +/- 18.52) and diastolic (from 94.37 +/- 19.70 to 79.31 +/- 7.87) blood pressures of these patients. The aim here is not to compare the effectiveness of acupuncture and drug therapy on blood pressure, but to simply report that on patients currently using antihypertensive medication, acupuncture facilitated a significant reduction in blood pressure and reduced the patients complaints. We therefore conclude that our data strongly suggest that acupuncture should be in the hypertension treatment guidelines and widely used for blood pressure regulation.

Treatment of nocturia symptoms with acupuncture.

Nocturia is a common symptom in the elderly. It causes sleeping disorders and is also associated with a higher risk of falling and increased mortality. The majority of nocturia patients prescribed desmopressin although it may cause significant hyponatremia which is a serious life threatening side effect. There is a need to use safer alternative treatment strategies specialy for older nocturia patients. We aim to examine the effect of acupuncture treatment on nocturia patients as a safe alternative treatment option. 35 nocturia patients have been joined to our study aged between 28 to 72. Among those patients in the study, 23 were female while 12 were male. Acupuncture treatment were applied in every 2 days totaling 10 sessions and each treatment session has lasted for 20 minutes. Nocturia frequency of the patients were recorded 1 to 6 before acupuncture treatment sessions. We have observed that nocturia symptoms recovered completely in 60% of the patients at the end of 10 sessions of the treatment while nocturia frequency were reduced to one per night in 37% of the patients. On the other hand nocturia sypmtoms in 2.8% of the patients were not changed at all. As a result 97% of the patients have responded to acupuncture treatment positively which applied bilaterally to Yintang point, Ki 3, Liv 3, Sp 9, L.I. 4, Ht 7, Sp 6, Lu 9, Sp 3, P 6 points. According to our results we conclude that acupuncture treatment should be widely used in nocturia patients of older ages as well as relatively younger adults.

Influence of acupuncture on leptin, ghrelin, insulin and cholecystokinin in obese women: a randomised, sham-controlled preliminary trial.

BACKGROUND: Obesity is an energy balance problem caused by overeating. Obesity treatment includes diet, exercise, behaviour treatment, pharmacotherapy and surgery; in addition, acupuncture is also an option. OBJECTIVE: To investigate the effect of acupuncture on weight loss and whether a brief acupuncture treatment of 5 weeks can change circulating levels of leptin, ghrelin, insulin and cholecystokinin (CCK) in obese women. METHODS: 40 women with a body mass index (BMI)>30 kg/m(2) were equally randomised to either an acupuncture group or a sham (non-penetrating) acupuncture group and received treatment at LI4, HT7, ST36, ST44 and SP6 bilaterally. Both groups had two sessions of 20 min/week for a total of 10 sessions. Serum insulin, leptin, plasma ghrelin and CCK levels were measured by ELISA. RESULTS: Acupuncture treatment decreased insulin and leptin levels and induced weight loss, together with a decrease in BMI compared with sham acupuncture. Furthermore, between-group analyses demonstrated increases in plasma ghrelin and CCK levels in subjects who received acupuncture treatment. CONCLUSION: These findings suggest that acupuncture may help to regulate weight owing to its beneficial effects on hormones such as insulin, leptin, ghrelin and CCK in obese subjects even after a few weeks of treatment.

The effects of acupuncture on the levels of blood pressure and nitric oxide in hypertensive patients.

Hypertension possess a significant risk factor for a variety of diseases and affects millions of people all around the world. Recent studies suggest that NO plays a role in pathogenesis of hypertension while some investigators find a close relationship between acupuncture treatment and NO levels. We therefore aimed to investigate the effect of acupuncture on the levels of blood pressure and nitric oxide (NO) in hypertensive patients. After obtaining institutional ethics committee approval and patients' informed consent, 32 essential hypertensive patients aged between 32-65 and taking antihypertensive drugs were included to the study. A total of 10 sessions of manual acupuncture were applied on body acupoints (EX-HN3 (Yintang), KI 3, LIV 3, SP 9, LI 4, HT 7, ST 36, SP 6) in 10 weeks. Systolic (SBP) and diastolic blood pressure (DBP) levels and blood NO levels were measured for 3 times (i.e. before & after the first session, and after the 10th session). Main outcome measures of our study were the changes in SBP and DBP as well as nitric oxide levels between 3 measurements were compared. Our study showed that SBP and DBP values decreased both after the 1st and 10th sessions of acupuncture treatments (p<0.05). The NO concentration also increased both after the 1st (71.5%) and 10th sessions (184.6%) (p<0.05).

In vitro effect of lemon and orange juices on calcium oxalate crystallization.

AIM: In recent years significant progress has been made in identifying and quantitating physico-chemical processes involved in urinary stone formation. The ability of urine to inhibit calcium oxalate crystallization is an important mechanism against stone formation. Dietary factors appear to affect the ability of urine to inhibit calcium oxalate crystallization. These factors encouraged us to study the effects of lemon and orange juices on calcium oxalate crystallization in vitro. MATERIAL AND METHODS: The nucleation and aggregation of calcium oxalate monohydrate crystals were studied using turbidimetric 30-min time course measurements of optic density at 620 nm after mixing solutions containing calcium chloride and sodium oxalate at 37 degrees C, pH 5.7. The formation of crystals is induced by the addition of the oxalate and calcium solution. The effects on calcium oxalate crystal growth of trisodium citrate, lemon and orange juices were examined. The effects of lemon and orange juices were evaluated by the addition of 50 ml of juices. The optical density is measured at physiological conditions. The maximum increase of optic density with time, termed SN, reflects maximum rate of formation of new particles. After an equilibrium has been reached, a progressive decrease of optic density with time is observed. Rate of aggregation, SA, is derived from the maximum decrease in optic density. RESULTS: Among the modifiers studied, citrate decreased both SN and SA (P<0.001). Lemon juice was also found to inhibit the rate of crystal nucleation and aggregation. But orange juice did not have any effect on the calcium oxalate crystallization (P>0.05). CONCLUSION: These results show that effective prevention of urinary stone formation should aim at restoring the urine's ability to inhibit calcium oxalate crystallization and more emphasis should be given to dietary measures.

Impact of various modifiers on calcium oxalate crystallization.

OBJECTIVE: This work focuses on the behavior of in vitro calcium oxalate crystallization. The effects of several compounds on the kinetics of calcium oxalate crystallization were examined. METHODS: Rates of nucleation and aggregation of calcium oxalate crystals were derived from 30-min time-course measurements of optic density at 620 nm after mixing solutions containing calcium chloride and sodium oxalate at 37 degrees C, pH 5.7. The maximum increase of optic density with time, termed S(N), mainly reflects maximum rate of formation of new particles and thus crystal nucleation. After equilibrium has been reached, optic density decreases. No new particles were formed due to crystal aggregation. S(A) (the maximum slope of decrease of optic density at 620 nm with time, representing crystal aggregation) is derived from the maximum decrease in optic density. RESULTS: Among the modifiers studied, citrate decreased both S(N) and S(A) (P < 0.001). Magnesium was also found to inhibit the rate of nucleation and crystal aggregation, but it appeared in a non-concentrated manner. Nucleation and aggregation inhibition ratios were related inversely to concentration of albumin (P < 0.001). CONCLUSION: The growth and agglomeration of calcium oxalate crystals are differently modulated by various compounds. The treatments aiming at inhibiting crystallization of calcium oxalate can be better defined by these findings. And new treatment modalities can be developed.

Effects of in vivo antioxidant enzyme activities of myrtle oil in normoglycaemic and alloxan diabetic rabbits.

In this study we aimed to evaluate the in vivo effects of myrtle oil (myrtii oleum) on the antioxidant enzymes such as superoxide dismutase and catalase, the levels of malondialdehyde in liver tissues as an index of lipid peroxidation and nitrite-nitrate levels in normoglycaemic and alloxan-induced diabetic and MO-treated rabbits. In our previous study, we assumed that MO with a dose of 50 mg/kg, possesses a hypoglycemic activity and this activity was independent from the effects of insulin. Myrtle oil exerts its hypoglycemic activity by enhanced glycolysis, glycogenesis and decreased glycogenolysis. What is more glucose load data strongly suggest that MO treatment produces hypoglycemia mainly by reducing intestinal absorption of glucose, so MO could be an alpha-glycosidase enzyme inhibitor which had a hypoglycaemic effect only on alloxan-induced diabetic rabbits on the fourth hour and on orally glucose loaded group. The major finding of this new study is that, MO may not offer any protection against oxidative stress during acute studies in normoglycemic and diabetic groups. Although the levels of superoxide dismutase and catalase enzyme activities did not change during acute studies in diabetes + MO group, there was a significant change at the end of 21 days. There is a very limited knowledge about MO and its effects on diabetes. Therefore, we tried to explain the mechanism that might underlie the protective effects of MO with this paper.

Effects of antioxidant stobadine on protein carbonylation, advanced oxidation protein products and reductive capacity of liver in streptozotocin-diabetic rats: role of oxidative/nitrosative stress.

BACKGROUND: Increased oxidative/nitrosative stress is important in the pathogenesis of diabetic complications, and the protective effects of antioxidants are a topic of intense research. The purpose of this study was to investigate whether a pyridoindole antioxidant stobadine (STB) have a protective effect on tissue oxidative protein damage represented by the parameters such as protein carbonylation (PC), protein thiol (P-SH), total thiol (T-SH) and non-protein thiol (Np-SH), nitrotyrosine (3-NT), and advanced oxidation protein products (AOPP) in streptozotocin-diabetic rats. METHODS: Diabetes was induced in male Wistar rats by intraperitonal injection of streptozotocin (55 mg/kg). Some of the non-diabetic (control) and diabetic rats treated with STB (24.7 mg/kg/day) during 16 weeks, and the effects on blood glucose, PC, AOPP, 3-NT, P-SH, T-SH and Np-SH were studied. Biomarkers were assayed by enzyme-linked immunosorbent assay (ELISA) or by colorimetric methods. RESULTS: Administration of stobadine to diabetic animals lowered elevated blood glucose levels by approximately 16% relative to untreated diabetic rats. Although stobadine decreased blood glucose, poor glycemic control was maintained in stobadine treated diabetic rats during the treatment period. Biochemical analyses of liver proteins showed significant diminution of sulfhydryl groups, P-SH, T-SH, Np-SH, and elevation of carbonyl groups in diabetic animals in comparison to healthy controls. As a biomarker of nitrosative stress, 3-NT levels did not significantly change by diabetes induction or by stobadine treatment when compared to control animals. However, the treatment with stobadine resulted in a significant decrease in PC, AOPP levels and normalized P-SH, T-SH, Np-SH groups in liver of diabetic animals. CONCLUSIONS: The results are in accordance with the pro-oxidant role of chronic hyperglycemia, and the ability of stobadine to attenuate protein oxidation and improving tissue reductive capacity may account, at least partly for its observed beneficial effects on tissue function in diabetes.

Hypoglycaemic effects of myrtle oil in normal and alloxan-diabetic rabbits.

Myrtus communis L. (Myrtaceae) leaves as well as the volatile oil (Myrtii Oleum; MO) obtained from the leaves are used to lower the blood glucose level in type-2 diabetic patients in Turkish folk medicine. However, little attention has been paid to the therapeutic use of this plant. The present study was designed to investigate the oral hypoglycaemic activity of single and multiple doses of MO in normal and alloxan-diabetic rabbits. MO did not show any effect in normoglycaemic rabbits either in single or multiple dose administrations, but a good hypoglycaemic activity was observed 4 h after the administration to diabetic animals at 50 mg/kg. To investigate the effect of MO on repeated administration in both normal and diabetic rabbits, it was administered in 50 and 100 mg/kg doses once a day for one week. MO significantly lowered blood glucose by 51% in alloxan-diabetic rabbits on the fourth hour and the following days at a dose of 50 mg/kg (P < 0.001). The hypoglycaemic dose (50 mg/kg) was also determined by performing the oral glucose tolerance test (OGTT) in normal rabbits. The hypoglycaemic effect of the MO was 21% higher in rabbits, which received the glucose load orally, when compared with control group. However, MO did not affect serum insulin concentrations in normal and alloxan-diabetic rabbits but reduced the serum triglyceride concentrations by 14% in alloxan-diabetic rabbits. The above observations show that MO exerts hypoglycaemic as well as mild hypotriglyceridemic activity in diabetic animals. The reduction in blood glucose level may be due to the reversible inhibition of alpha-glucosidases present in the brush-border of the small intestinal mucosa, higher rate of glycolysis as envisaged by the higher activity of glucokinase, as one of the key enzymes of glycolysis, and enhanced rate of glycogenesis as evidenced by the higher amount of liver glycogen present after MO administration.

Effect of Calcium Entry Blocking Agents (Nifedipine and Verapamil) on Myocardial Recovery during Reperfusion.

A comparative study on isolated guinea pig hearts was carried out to determine the effect of calcium entry blocking agents: nifedipine- and verapamil-added reperfusion solutions on myocardial recovery after global ischemia. After 20 min of normothermic ischemia, three groups of solutions were used for reperfusion (10 animals each): (1) Nifedipine-added (10--8 mmol L(minus sign1)) Krebs--Henseleit solution; (2) verapamil-added (10--8 mmol L(minus sign)) Krebs-Henseleit solution; (3) Krebs--Henseleit solution. Postischemic myocardial functions (ventricular contractile force and heart work) and enzyme activities were compared with their preischemic values. The addition of calcium entry blocking agents does not have any significant advantage over control solutions in myocardial recovery.