Agmatine co‐treatment attenuates allodynia and structural abnormalities in cisplatin‐induced neuropathy in rats

Cisplatin is a widely used antineoplastic agent in the treatment of various cancers. Peripheral neuropathy is a well‐known side effect of cisplatin and has potential to result in limiting and/or reducing the dose, decreasing the quality of life. Thus, effective treatments are needed. Agmatine is an endogenous neuromodulator that has been shown to exert antiallodynic effects in various animal studies. The first aim of this study was to investigate the in vitro effects of agmatine on cisplatin‐induced neurotoxicity. Primary cultures of dorsal root ganglia (DRG) which are the primary target of drug injury were prepared. DRG cells were incubated with cisplatin (100, 200, 500 μm ). Then, agmatine (10, 100, 500 μm ) was administered with the submaximal concentration of cisplatin. Cisplatin caused concentration‐dependent neurotoxicity, and agmatine did not alter this effect. The second aim was to investigate the effects of agmatine on cisplatin‐induced peripheral neuropathy in rats and the influence of nitric oxide synthase (NOS) inhibitor, L‐NAME, in this effect. Female Sprague Dawley rats received intraperitoneal saline (control), cisplatin (3 mg/kg), cisplatin+agmatine (100 mg/kg), or cisplatin+agmatine+L‐NAME (10 mg/kg) once a week for 5 weeks. The mechanical allodynia, hot plate, and tail clip tests were performed, and DRG cells and sciatic nerves were analyzed. Agmatine and agmatine+L‐NAME combination attenuated CIS‐induced mechanical allodynia and degeneration in DRG cells and sciatic nerves. However, L‐NAME did not potentiate the antiallodynic or neuroprotective effect of agmatine. These findings indicate that agmatine co‐administration ameliorates cisplatin‐induced neuropathy and may be a therapeutic alternative.     

Inhibition of dentin matrix‐bound cysteine cathepsins by potassium fluoride

Matrix metalloproteinases (MMPs) and cysteine cathepsins (CCs) can break down unprotected type I collagen fibrils in dentin matrix. This study investigated the use of potassium fluoride (KF) as a potential inhibitor of MMPs and CCs in dentin. Demineralized dentin beams were divided into groups (n = 10 in each group) and incubated in artificial saliva (AS, control), either alone or with one of seven concentrations of KF (6–238 mM fluoride) for 1, 7, and 21 d. After 21 d, all groups were further aged in AS for 6 months. Total MMP activity was screened using the colorimetric MMP assay. The activities of MMP‐2 and MMP‐9 were investigated using gelatin zymography. At the end of each incubation, changes in loss of dry mass and CC‐mediated or total dissolution of collagen peptides were measured via precision weighing, C‐terminal crosslinked telopeptide of type I collagen (CTX), and hydroxyproline (HYP) assays. The beams were examined using scanning electron microscopy. After 21 d, total MMP activities, dry mass loss, and CTX release for the groups exposed to 179 and 238 mM fluoride were significantly lower compared with the control group. After 6 months, all groups showed similar total MMP activity, dry mass loss, and HYP release, and CTX levels were significantly lower when the fluoride concentration was ≥24 mM. Calcium fluoride (CaF₂)‐like precipitates were observed over the beams. In summary, KF significantly inhibited the catalytic activity of dentin matrix‐bound CCs but did not seem to be effective for MMP‐mediated activity.     

The Turkish Version of the Auditory Consonant Trigram Test as a Measure of Working Memory: A Normative Study

The following study was conducted to adapt the Auditory Consonant Trigram Test (ACT) to Turkish, acquire a new and larger set of normative data, and finally investigate the reliability and validity of the adapted version. The data were collected from a sample of 236 healthy individuals. To test the validity of the Turkish version of ACT, the normative results of ACT were first compared with those obtained from the Digit Span Test (DST) backwards section. Secondly, the ACT performance of 53 schizophrenic patients was compared with that of a matched group selected from the normative sample. Age and education variables influenced performance, whereas gender did not in the normal sample. The ACT and DST backwards scores were positively correlated. As expected, the ACT performance was worse in schizophrenic patients compared to controls. The internal consistency of the adapted version of ACT was found to be at a reliable level (a=0.8535). The Turkish version of ACT can be considered to be a reliable and valid measure of working memory.     

The effects of dexamethasone and levobupivacaine on postoperative pain in Modified Radiofrequency Assisted Uvulopalatoplasty (MRAUP) surgery

The objective of this prospective, randomized study was to evaluate the effect of pre-emptive local infiltration of lidocaine, lidocaine plus dexamethasone, levobupivacaine and levobupivacaine plus dexamethasone on postoperative pain in Modified Radiofrequency Assisted Uvulopalatoplasty (MRAUP) cases. Sixty adult patients (44 males and 16 females) aged 32–51 years with simple snoring were divided into four groups. The anesthesia of the patients in the first group was achieved with lidocaine HCl, in the second group, with lidocaine HCl and dexamethasone sodium phosphate, in the third group, with levobupivacaine, and in the fourth group, levobupivacaine and dexamethasone sodium phosphate. All the patients were applied Modified Radiofrequency Assisted Uvulopalatoplasty technique. The pain experienced by the patients during swallowing and at rest on the 1st, 3rd, 5th, 7th, and 10th day and analgesic consumption were evaluated using standard 10 cm visual analog scales. The mean duration of operation in the group that received lidocaine HCl was 22 ± 3 min, while in the group that received levobupivacaine HCl was 27 ± 4 min. There were statistically significant differences between the groups for analgesic effects on the 1st, 3rd, 5th, and 7th day and for the amount of analgesics used, on the 1st, 3rd, and 5th day. The best results were obtained in the group that received levobupivacaine HCl and steroid (p < 0.001). Steroid and local anesthetic combinations are superior to controls in the management of postoperative pain in MRAUP surgery.     

A pyridoindole antioxidant SMe1EC2 regulates contractility,relaxation ability,cation channel activity,and protein-carbonyl modifications in the aorta of young and old rats with or without diabetes mellitus

We studied the effects of treatment with SMe1EC, a hexahydropyridoindole antioxidant, on vascular reactivity, endothelial function, and oxidonitrosative stress level of thoracic aorta in young and old rats with or without diabetes mellitus. The rats were grouped as young control (YC 3 months old), old control (OC 15 months old), young diabetic (YD), old diabetic (OD), young control treated (YCT), old control treated (OCT), young diabetic treated (YDT), and old diabetic treated (ODT). Diabetes was induced by streptozotocin injection and subsequently SMe1EC2 (10 mg/kg/day, p.o.) was administered to YCT, OCT, YDT, and ODT rats for 5 months. In young and old rats, diabetes resulted in hypertension, weight loss, hyperglycemia, and hypertriglyceridemia, which were partially prevented by SMe1EC2. SMe1EC2 also inhibited the diabetes-induced increase in aorta levels of AGEs (advanced glycosylation end-protein adducts), 4-HNE (4-hydroxy-nonenal-histidine), 3-NT (3-nitrotyrosine), and RAGEs (receptors for AGEs). The contractions of the aorta rings to phenylephrine (Phe) and KCL did not significantly change, but acetylcholine (ACh) and salbutamol relaxations were reduced in OC compared to YC rats. Diabetes induction increased Phe contractions in YC and OC rats, KCL contractions in YC rats, and did not cause further inhibition in already inhibited ACh and salbutamol relaxations in OC rats. We have achieved the lowest levels of ACh relaxation in YD rats compared to other groups. SMe1EC2 did not change the response of aorta to ACh, salbutamol and Phe in YC rats, and ameliorated ACh relaxations in OC and YD but not in OD rats. In YDT and ODT rats, increased Phe and KCL contractions, high blood pressure, and impaired salbutamol relaxations were amended by SMe1EC2. Phe contractions observed in YD and OD rats as well as KCl contractions observed in OC rats were the lowest levels when the rats were treated with SMe1EC2. When the bath solution was shifted to cyclopiazonic acid (CYP) or CYP plus Ca²⁺-free medium, the contraction induced by a single dose of Phe (3?×?10^?6 M) was more inhibited in YD and OD than in YC but not in OC rats. In SMe1EC2-treated rats, neither the presence of CFM nor CFM plus CYP exhibited a significant change in response of aorta to a single dose of Phe. These findings suggest that α1-adrenergic receptor signaling is activated in both age groups of diabetic rats, diabetes activates K⁺-depolarization and calcium mobilization via Ca_V especially in the aorta of young rats, and sensitizes the aorta of old rats to the regulating effect of SMe1EC2. ACh relaxations were inhibited in YC rats, increased in OC rats and unchanged in YD and OD rats when aortic rings pretreated with TEA, an inhibitor of calcium-activated K⁺ channels (K_Ca), or 4-aminopyridine (4-AP), an inhibitor of voltage-sensitive K⁺ channels (K_V). ACh relaxations were inhibited in YCT, OCT, and YDT rats in the presence of 4-AP or TEA. In ODT rats, 4-AP did not change ACh relaxation but TEA inhibited. These findings suggest that the contribution of K_v and K_Ca to ACh relaxation is likely upregulated by SMe1EC2 when the relaxations were inhibited by aging or diabetes. We conclude that SMe1EC2 might be a promising agent for aging and diabetes related vascular disorders.     

A rare cause of acute abdominal pain in adolescence: Hydrosalpinx leading to isolated torsion of fallopian tube

Torsion of the fallopian tube accompanying hydrosalpinx is a rare occurrence in the pediatric population. This report describes a 13 year old sexually inactive girl with isolated tubal torsion due to hydrosalpinx. The girl had lower left abdominal pain for two days. The physical examination revealed left lower quadrant tenderness with a firm round anterior mass on rectal examination. Abdominal ultrasound showed left tubal enlargement with free pelvic peritoneal fluid. Magnetic Resonance Imaging (MRI) showed engorgement and dilatation of the left fallopian tube without contrast enhancement suspicious of tubal torsion. At operation, torsion of the left tube on its longitudinal axis was observed, and a salpingectomy was performed.     

Development of amyloidosis in Behçet's syndrome with isolated mucocutaneous involvement

Development of secondary amyloidosis is an infrequent complication in patients with Behçet's syndrome (BS). It has been reported that multiple systemic involvement, long disease duration, and male gender are major clinical factors accompanying the development of amyloidosis in BS. We report a case of secondary amyloidosis in a patient diagnosed as having BS with a positive pathergy test 9 years previously and who had isolated mucocutaneous involvement. Regular use of colchicine since the diagnosis and somewhat mild progress of the disease could not prevent the development of secondary amyloidosis in this patient. He is alive and receives hemodialysis regularly.