4-Methylthiobenzoic Acid Protection against Cisplatin Nephrotoxicity: Antioxidant System

This study investigates the changes in renal antioxidant systemafter cisplatin administration and the nephroprotection with4-methylthiobenzoic acid (MTBA). Male Wistar rats were injectedwith (1) vehicle control, (2) cisplatin, (3) MTBA, and (4) cisplatinplus MTBA. Rats were euthenized 3 days post-treatment and kidneywas isolated and analyzed for platinum concentration, malondialdehyde (MDA), glutathione (GSH and GSSG), superoxide dismutase(SOD), catalase (CAT), and glutathione peroxidase (GSH-Px).Plasma creatinine increased 508% following cisplatin administrationalone, which decreased to 189% with MTBA. Cisplatin-treatedrats showed a depletion of renal GSH levels (53%), while cisplatinplus MTBA-injected rats had GSH values close to those of thecontrols. SOD, CAT, and GSH-Px activities decreased 36, 29,and 38%, respectively, and MDA levels increased 212% followingcisplatin administration, which were restored to control levelsafter MTBA treatment. The renal platinum level depleted significantlywith MTBA treatment. The data suggest that cisplatin nephrotoxicityis mediated by depletion in GSH concentration and by impairedactivities of SOD, CAT, and GSH-Px, increased lipid peroxidation,and plasma creatinine levels. The protection offered by MTBAagainst cisplatin nephrotoxicity is related to the reductionin plasma creatinine levels, prevention of GSH depletion andlipid peroxidation, and restoring antioxidant enzyme activityin the kidneys of rats.     

T Lymphocyte Subsets in Parenteral and Non-parenteral Heroin Abusers in Britain

Parenteral drug abusers comprise the second largest group of patients with the acquired immune deficiency syndrome (AIDS). To determine whether heroin abusers in Britain had immunologic abnormalities similar to those seen in AIDS, we determined T lymphocyte subsets in 14 parenteral heroin abusers and 10 non-parenteral heroin abusers. No significant differences were found in T4/T8 ratios or in the absolute numbers of T3, T4, or T8-positive cells. These results suggest that neither narcotic drugs nor repeated exposure to unsterile injectable substances are responsible for low T4/T8 ratios in parenteral drug abusers with AIDS.     

CHANGES IN LEVELS OF CARTILAGE OLIGOMERIC PROTEINASE AND URINARY C-TERMINAL TELOPEPTIDE OF TYPE II COLLAGEN IN SUBJECTS WITH KNEE OSTEOARTHRITIS AFTER DEXTROSE PROLOTHERAPY: A RANDOMIZED CONTROLLED TRIAL

ObjectiveTo assess the effects of dextrose prolotherapy in patients with knee osteoarthritis on the levels of serum cartilage oligomeric proteinase and urinary C-terminal telopeptide of type II collagen, and on the Western Ontario McMaster Universities Index and numerical rating scale score for pain.MethodsA randomized controlled trial, in which participants were randomly allocated into 2 groups, receiving injections of either hyaluronic acid or dextrose prolotherapy. The hyaluronic acid group received 5 injections, 1 each on weeks 1, 2, 3, 4 and 5, and the dextrose prolotherapy group received 3 injections, 1 each on weeks 1, 5 and 9. Serum cartilage oligomeric proteinase, urinary C-terminal telopeptide of type II collagen, Western Ontario McMaster Universities Index score, and numerical rating scale score for pain were measured at baseline and 3 weeks after the last injection. Comparative analysis was conducted using Wilcoxon test within groups and analysis of covariance (ANCOVA) test between groups.ResultsA total of 47 participants (21 allocated to hyaluronic acid, 26 allocated to dextrose prolotherapy) completed the protocol. Both interventions resulted in significant improvements in numerical rating scale scores for pain, total Western Ontario McMaster Universities Index scores, and its subscales score. However, the dextrose prolotherapy outperformed hyaluronic acid in numerical rating scale score for pain and level of urinary C-terminal telopeptide of type II collagen, with score changes differences of 0.93 (p = 0.042) and 0.34 (p = 0.048), respectively. No significant changes in level of serum cartilage oligomeric proteinase were found in either group.ConclusionDextrose prolotherapy is an alternative injection therapy for knee osteoarthritis, which was found to be associated with a significant reduction in urinary C-terminal telopeptide of type II collagen compared with hyaluronic acid injection. Neither injection method resulted in reduced serum cartilage oligomeric proteinase.LAY ABSTRACTKnee osteoarthritis is a common musculoskeletal disorder, which is one of the most frequent causes of disability in elderly people. To improve patients’ quality of life, prolotherapy has been developed as a non-operative treatment option for osteoarthritis. This study compared the effectiveness of dextrose prolotherapy with that of standard therapy using hyaluronic acid injections. Both interventions were effective in terms of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score improvement and numerical rating scale score changes. Cartilage repair was assessed by measuring levels of specific biomarkers of cartilage breakdown: urinary C-terminal telopeptide of type II collagen (uCTX-II) and serum cartilage oligomeric matrix protein (sCOMP). Dextrose prolotherapy was more effective than hyaluronic acid in reducing these biomarkers and decreasing patients’ pain. Dextrose prolotherapy is therefore recommended for use in patients with knee osteoarthritis, since it gives better results, is cost beneficial, and is suitable for use in low-resource settings. Dextrose prolotherapy may help to repair cartilage in knee OA, as it reduces the uCTX-II level.Key words: knee osteoarthritis, prolotherapy, hyaluronic acid, COMP, uCTX-II, functional outcome

Osteoarthritis (OA) is a highly prevalent musculoskeletal disorder, which is one of the most common causes of disability in elderly people (1–3). Several studies have demonstrated the effectiveness of hyaluronic acid (HA) injections, and recent guidelines have recommended their use in knee OA (4, 5). Xin has shown that intra-articular injection of HA (Adant®, Meiji Seika Pharma Co., Ltd., Tokyo, Japan. Manufactured by microbial fermentation and Artz®, Dispo: Seikagaku Corporation, Tokyo, Japan. Manufactured by the extraction of cockscomb), can significantly reduce both the visual analogue scale (VAS) score for pain and the Lequesne index (6). In contrast to these findings, however, a meta-analysis concluded that treatment of knee OA with HA injection did not result in a significantly different outcome from intra-articular placebo, despite the higher costs compared with other common non-operative intra-articular modalities (7).Regenerative therapy is an alternative approach that has been considered for OA, due to its potential to aid tissue regeneration, improve clinical manifestations, and repair damaged tissue structure, which is the underlying pathological condition in OA (8). An example of a currently developing regenerative approach is prolotherapy, an injection-based modality for treating chronic musculoskeletal pain through the use of substances such as dextrose, phenol-glycerine-glucose (P2G), or sodium morrhuate (9). Previous reports have demonstrated the effectivity of prolotherapy in significantly reducing the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score relative to saline injections and at-home exercise over 18 weeks after injection (10–12). In line with these findings, other reports have shown the promising effects of prolotherapy for tissue regeneration through radiological and arthroscopy-based assessments of cartilage repair (13).Cartilage oligomeric matrix protein (COMP) and urinary C-terminal telopeptide of type II collagen (uCTX-II) are specific biomarkers used to evaluate cartilage break-down in OA. Increased levels of these biomarkers can indicate the severity and prognosis of OA(14). Meanwhile, decrease in levels of both biomarkers has been assumed which indicates the improvement in cartilage (15). COMP and uCTX-II are recommended as promising specific bio-markers in OAcases based on Burden of disease, Investigative, prognostic, efficacy of intervention, and diagnostic (BIPED) criteria, as stated in a systematic review (16).Although previous reports have demonstrated promising potential of HA-based therapy and dextrose prolotherapy (DPT) in improving functional outcome in knee OA, none have compared the efficacy of those modalities in cartilage repair by assessing specific biomarkers, such as serum COMP (sCOMP) and uCTX-II. Hence, the aim of this study was to compare the effects of intra-articular HAand DPT on cartilage repair in knee OA, by measuring the changes in sCOMP and uCTX-II biomarkers.     

Peptide-lanthanide cation equilibria in aqueous solution

Lanthanide ion complexes of α-L-aspartyl-L-phenylalanine methyl ester have been characterized in the pH range 2.50-7.00. Proton resonance shifts in D₂O and DMSO were used to determine the conformational mobility and a tentative structure in solution is proposed. The observed trends in the magnitude of the shift ratios and the rotamer population suggested that the metal ion Pr(III) or Dy(III) bound to the carboxylate group and gave information about the peptide backbone. The result of this analysis has been used to select a preferential conformation of the molecule: ø₁? 60d?, φ₂? -150d?, C^βCγLn = 140d?± 10d?, C^αC^βC^γLn = 10d?± 20d? (hindered rotation), Cγ-Ln = 2.85Ad?± 0.1Ad?.     

The effect of dentine thickness on diffusion of resin monomers in vitro

summary Forty extracted human third molar teeth were divided into four groups, each of 10 teeth, to test the hypothesis that dentine thickness variation influences diffusion of the monomers 2-hydroxy-ethylmethacrylate (HEMA) and triethylene glycol dimethacrylate (TEGDMA) from light-cured bonding resin-composite resin restorations to the pulp space. An occlusal cavity 6 mm in diameter was prepared in each tooth of four groups with remaining dentine thickness of 3.4–3.6, 2.4–2.6, 1.4–1.6 and 0.4–0.6 mm, respectively. A polypropylene chamber was attached to the cemento-enamel junction of each tooth to contain I mL of distilled water. Each cavity was treated with Scotchbond Multipurpose (3m, U.S.A.) then restored with Z100 (3m) and light activated for 30 s. Water samples were retrieved over a time course up to 30 days and analysed by high performance liquid chromatography. Both HEMA and TEGDMA were detected in the pulp samples for all teeth. Decreasing dentine thickness substantially increased pulpward diffusion rate of both HEMA and TEGDMA during the first day after placement, as well as the total release of both components from a bonding resin-composite combination in vitro .     

Electrophysiological Effects of atrial Natriuretic Peptide on the Cardiac Conduction System in Man

We assessed the effect of atrial natriuretic peptide (ANP) on electrophysiological parameters in man. Electrophysiological parameters were measured before, at 15, and at 30 minutes after the commencement of ANP or placebo infusions (six patients in each group). ANP levels were normal prior to infusion and rose with ANP to 159 ± 43 pmol/L, but were stable during placebo infusion. No change in heart rate or blood pressure occurred in either group. ANP infusion resulted in significant falls in intraatrial conduction time (60 ± 15 to 49 ± 15 msec), PR interval (170 ± 21 to 155 ± 16 msec), right atrial effective refractory period (232 ± 33 to 218 ± 33 msec), and ventriculoatrial refractory period (452 ± 148 to 393 ± 183 msec) while no change was seen with placebo. We conclude that ANP infusion appears to affect atrial refractoriness and velocity of conduction and atrioventricular nodal refractoriness. However, the mechanism of action and clinical significance of this observation remain to be determined.     

Immunocytochemical characterization of neuroendocrine tumours of the larynx

Twenty-two neuroendocrine tumours of the larynx were investigated using a panel of immunocytochemical markers. Three were small cell carcinomas, eight were large cell neuroendocrine carcinomas and 11 were paragangliomas. Twenty were positive for protein gene product 9.5, 19 for neuron-specific enolase, 15 for chromogranin A, nine for bombesin, eight for substance P, eight for neuropeptide Y, eight for metenkephalin, seven for somatostatin, five for calcitonin, eight for calcitonin gene-related peptide and one for vasoactive intestinal polypeptide. Bombesin immunoreactivity was largely restricted to the small cell carcinomas and large cell neuroendocrine carcinomas and neuropeptide Y, metenkephalin and substance P to the parangangliomas. This comprehensive immunocytochemical analysis of neuroendocrine tumours of the larynx demonstrates that these tumours represent special entities but have similar patterns of immunostaining to those of neuroendocrine tumours in other sites.