Semiquinone derivative isolated from Bacillus sp. INM-1 protects cellular antioxidant enzymes from γ-radiation-induced renal toxicity.

This study was focused to evaluate protection of indigenous antioxidant system of mice against gamma radiation-induced oxidative stress using a semiquinone (SQGD)-rich fraction isolated from Bacillus sp. INM-1. Male C57bl/6 mice were administered SQGD (50 mg/kgb.w.i.p.) 2 h before irradiation (10 Gy) and modulation in antioxidant enzymes activities was estimated at different time intervals and compared with irradiated mice which were not pretreated by SQGD. Compared to untreated controls, SQGD pretreatment significantly (p < 0.05) accelerates superoxide dismutase, catalase, GSH, and glutathione-S-transferase activities. Similarly, significant (p < 0.05) increase in the expression of superoxide dismutase, catalase, GSH, and glutathione-S-transferase was observed in irradiated mice pretreated by SQGD, compared to only irradiated groups. Total antioxidant status equivalent to trolox was estimated in renal tissue of the mice after SQGD administration. Significant ABTS(+) radical formation was observed in H2O2-treated kidney homogenate, due to oxidative stress in the tissue. However, significant decrease in the levels of ABTS(+) radical was observed in kidney homogenate of the mice pretreated with SQGD. Therefore, it can be concluded that SQGD neutralizes oxidative stress by induction of antioxidant enzymes activities and thus improved total antioxidant status in cellular system and hence contributes to radioprotection.

Tailoring deformation and superelastic behaviors of beta-type Ti-Nb-Mn-Sn alloys.

A group of Ti-25Nb-xMn-ySn (in wt%; x = 2, 4 and y = 1, 5) alloys were designed using the "BF-d-electron superelasticity" empirical relationship and subsequently were cast in order to investigate their microstructure, deformation and superelastic behaviors. Monolithic ß phase is found in all investigated alloys except in Ti-25Nb-2Mn-1Sn alloy which exhibits α"+ß dual-phase microstructure. During compression testing, the Ti-25Nb-2Mn-1Sn alloy fails and demonstrates sufficient plasticity of ~ 41% and ultimate compressive strength of ~ 1800 MPa, where other alloys do not fail within the load capacity of 100 kN. Among all the investigated alloys, Ti-25Nb-4Mn-1Sn alloy exhibits the highest yield strength (~ 710 MPa) while Ti-25Nb-2Mn-1Sn alloy possesses the highest hardness (~ 244 HV). In this work, yield strength is influenced by solid solution and grain boundary strengthening while hardness is affected by the amount of constituent phases in each alloy. Additionally, Ti-25Nb-4Mn-1Sn shows highest recoverable strain (2.35%) and superelastic recovery ratio (90%) during cyclic loading-unloading up to 3% strain level, with highest total energy absorption among the investigated alloys. Moreover, all the Ti-25Nb-xMn-ySn alloys display shear bands except that Ti-25Nb-2Mn-1Sn alloy displays shear bands together with some cracks on the outer surface of compressively deformed morphologies.

Strengthening mechanism and corrosion resistance of beta-type Ti-Nb-Zr-Mn alloys.

In order to achieve an effective balance between plasticity and strength, a group of Ti-26Nb-xZr-yMn (x = 4, 7, 10 wt% and y = 3, 5 wt%) alloys were designed to evaluate the effects of Mn and Zr on the microstructures, mechanical properties and strengthening effects of the TiNb system. All the investigated alloys illustrate a monolithic ß phase in their microstructure and they all possess substantial true plasticity (~160%) and true maximum strength (~ 950 MPa) without fracture during the compression tests within the load capacity of 100 kN. The contribution of solid-solution, grain-boundary and dislocation strengthening mechanisms have been evaluated using the strengthening model for ß Ti alloys for all the investigated alloys. Among the investigated alloys, Ti-26Nb-4Zr-5Mn demonstrates the highest true yield strength (654 MPa), dislocation density (2.45 × 1015 m-2) and hardness (242 HV) along with improved strain hardening ability in terms of strain hardening indices (0.42 and 0.09). Furthermore, based on the superior mechanical properties among the investigated alloys, the electrochemical performance of Ti-26Nb-4Zr-3Mn and Ti-26Nb-4Zr-5Mn have also been analyzed in this work. The electrochemical measurements show that both alloys have almost similar corrosion potential and corrosion current density in simulated body fluid, i.e., -0.45 V and 0.838 nA/cm2 for Ti-26Nb-4Zr-3Mn, -0.48 V and 0.839 nA/cm2 for Ti-26Nb-4Zr-5Mn, respectively.

Apoptosis is an early event during phthalocyanine photodynamic therapy-induced ablation of chemically induced squamous papillomas in mouse skin.

Photodynamic therapy (PDT) is a promising new modality to treat malignant neoplasms including superficial skin cancers. In our search for an ideal photosensitizer for PDT, Pc 4, a silicon phthalocyanine, has shown promising results both in in vitro assays and in implanted tumors. In this study we assessed the efficacy of Pc 4 PDT in the ablation of murine skin tumors; and the evidence for apoptosis during tumor ablation was also obtained. The Pc 4 was administered through tail vein injection to SENCAR mice bearing chemically induced squamous papillomas, and 24 h later the lesions were illuminated with an argon ion-pumped dye laser tuned at 675 nm for a total light dose of 135 J/cm2. Within 72-96 h, almost complete tumor shrinkage occurred; no tumor regrowth was observed up to 90 days post-PDT. As evident by nucleosome-size DNA fragmentation, appearance of apoptotic bodies in hematoxylin and eosin staining and direct immunoperoxidase detection of digoxigenin-labeled genomic DNA in sections, apoptosis was clearly evident 6 h post-PDT at which time tumor shrinkage was less than 30%. The apoptotic bodies, as evident by the condensation of chromatin material around the periphery of the nucleus and increased vacuolization of the cytoplasm, were also observed in electron microscopic studies of the tumor tissues following Pc 4 PDT. The extent of apoptosis was greater at 15 h than at 6 and 10 h post-PDT. Taken together, our results clearly show that Pc 4 may be an effective photosensitizer for PDT of nonmelanoma skin cancer, and that apoptosis is an early event during this process.

A population study of the screening potential of assessment of trabecular pattern of the femoral neck (Singh index): the Chingford Study.

The trabecular pattern of the femoral neck (Singh index) has been used as a measure of osteopenia and fracture risk but the value of this method is controversial. This study assessed the usefulness of the Singh index (SI) by using dual energy X-ray absorptiometry (DXA) as the "gold standard". 659 Caucasian women (45-70 years) from an age-sex register of a general practice had their femoral neck and lumbar spine bone densities measured by DXA and had antero-posterior hip X-rays performed which were then categorized into six osteopenia grades using the SI method. The intraobserver and interobserver reproducibility of this method was good (kappa = 0.64 and 0.61, respectively). The SI grades correlated significantly with body mass index (r = 0.35) and age (r = 0.17) (p < 0.001). The mean femoral neck and lumbar spine bone densities were significantly higher with increasing SI grade even after adjustment for age and body mass index (p < 0.001). The proportion of subjects below the fracture threshold (2 SD below mean peak bone mass) decreased with increasing SI grade, ranging from 100% in SI grade 2 to 16.8% in SI grade 6. There was, however, wide overlap of bone densities between the grades. Using the criteria "osteoporosis < or = SI grade 4", the sensitivity and specificity of the SI method diagnosing low bone mass was 35.1% and 90.0%, respectively. These data suggest that the SI is a reproducible tool which may detect differences in bone mass between populations or subgroups within populations, although caution should be used in classifying individual patients because of the wide variation in bone density. The method has a low sensitivity but a relatively high specificity in diagnosing low bone mass.

Why do we need new treatments for rheumatoid arthritis?

Rheumatoid arthritis is a chronic systemic autoimmune inflammatory disease characterized by progressive joint damage. The classical treatments of the disease such as myocrisin and sulphasalazine, are not always effective at controlling the disease. This has necessitated the development of novel agents for treating rheumatoid arthritis. Most of these drugs are biological in nature and are targeted at specific sites of the inflammatory cascade of reactions. A number of clinical trials have been conducted. The clinical effects that have been observed are transient, necessitating repeated treatments and the risk of vaccination effects. Many of these agents have to be administered parenterally, production costs are very high. Consequently, chemical entities which can be taken orally need to be developed. Since the immune system is very complex with pleiotropic cytokines and redundancy in some of the regulatory networks, it may therefore be necessary to use multiple agents targeted at different specific sites of the inflammatory cascade or that different agents could be given at different stages of the disease, to induce disease remission and maintain the response to therapy. Cytokines such as tumour necrosis factor (TNF) and interleukin 1 (IL-1) play important physiological roles in the host's defence systems against infections and malignancy. The chronic inhibition of these cytokines by targeted therapies may therefore lead to the development of side effects. Thus, carefully controlled long-term studies will be required to assess the safety of selective targeting of processes involved in inflammation. A more recent novel approach is to target hypoxic tissues with bioreductive agents. Thus, some of the established rheumatoid arthritis treatments could be linked to bioreductive agents and released in hypoxic tissues where inflammation is occurring. This review summarizes the important developments in the therapy of rheumatoid arthritis. There is no doubt that despite these developments we need to develop new and advanced treatment modalities for rheumatoid arthritis.

A survey of psychiatrically ill Asian children.

This case-note survey compares a group of Asian children referred to child psychiatry and guidance clinics in Bolton with a control group of white children referred to the same clinics. The proportion of Asian children was less than the proportion of Asian people in the general population. The proportion of Asian children coming from a broken home or a single-parent family was significantly lower than in the control group. Conduct disorders were more common in the control group and somatoform disorders were more common in the Asian group.

Tardive dyskinesia with schizophrenic relapse.

A case of a borderline subnormal schizophrenic is described in a patient who developed tardive dyskinesia after 21 years of neuroleptic therapy. However, features of tardive dyskinesia manifested only during the psychotic relapses and disappeared on remission of psychotic symptoms.

Quantitative heel ultrasound variables in powerlifters and controls.

OBJECTIVE: To compare by cross sectional study the quantitative heel ultrasound (QUS) variables broadband ultrasound attenuation (BUA) and velocity of sound (VOS) in male powerlifters and controls. METHODS: Twenty four powerlifters and 21 sedentary male controls were recruited to the study. All the powerlifters were members of the British Drug Free Powerlifting Association and actively competing at the time of the study. A questionnaire was completed by all those entered into the study. This included a history of smoking and an estimation of daily intake of alcohol and calcium. For the powerlifters, the number of years spent training and time spent training each week was also recorded. The QUS variables of all powerlifters and controls were measured using a Cubaclinical II (McCue) ultrasound scanner. RESULTS: The powerlifters had been training for a mean (SEM) of 10.6 (1.6) years and they trained for 6.5 (0.4) hours a week. The powerlifters were non-significantly older and had a significantly higher body mass index (BMI) than the controls. Calcium intake and consumption of alcohol and tobacco were similar in the two groups. The mean BUA in the powerlifters was a significant 9.5% (95% confidence interval 0.7 to 18.3%) higher than the controls (105 v 96 dB/MHZ) and 15.6% (95% confidence interval 6.8 to 24.4%) higher after adjustment using analysis of covariance for age, BMI, and alcohol and tobacco consumption (108 v 93 dB/MHZ). The mean VOS was similar in the two groups, but after adjustment it was significantly higher in the powerlifters (1671 v 1651 m/s, p<0.01). CONCLUSIONS: The study shows the ability of heel ultrasound to discriminate between QUS variables in powerlifters and controls. The results indicate that the QUS variables BUA and VOS are significantly higher for powerlifters than for controls.

Intra-articular pressure profile of the knee joint in a spectrum of inflammatory arthropathies.

OBJECTIVES: The intra-articular pressure (IAP) rises significantly after isometric quadriceps contraction in patients with rheumatoid synovitis, a process that may temporarily impede synovial blood flow and cause oxidative injury. In acute traumatic knee effusions (ATE) pressure rises are trivial. This study compared the IAP profiles of patients with ATE with three different populations--an acute synovitis on the background of a chronic inflammatory arthropathy, a chronic low grade inflammatory arthropathy, and an acute intermittent inflammatory arthropathy. The study objective was to discover if the pressure profiles observed in these groups reflect an influence of the inflammatory process or time or both. METHODS: Thirty three patients were studied. These were divided into four subgroups; group 1: five acute traumatic knee effusions (ATE); group 2: acute effusions on the background of a chronic inflammatory arthropathy: seven rheumatoid arthritis (RA), five psoriatic arthritis (PsA); group 3: seven osteoarthritis (OA) and group 4: acute effusions on the background of an intermittent inflammatory arthropathy: seven pyrophosphate arthropathy (PA), one amyloid (AA), one Behcet's (B). IAP was measured (mm Hg) at rest and during isometric quadriceps contraction using the hand held portable 295-1 intra-compartmental pressure monitor system (Stryker UK). The volume of synovial fluid aspirated was recorded. RESULTS: Expressed as medians (inter-quartile range). Resting IAP was; ATE 6 (2-12), RA 8 (5-47), PsA 18 (11-31), OA 17 (7-21), PA 25 (9-29), AA 14, and B 12. IAP increased in all subjects during isometric contraction; ATE 9 (7-16), RA 56 (33-150), PsA 52 (43-85), OA 56 (20-116), PA 53 (41-65), AA 47, B 57 and the IAP rise was significant (p < 0.05) in all except the ATE group (p > 0.05). The volume of synovial fluid aspirated in groups 2, 3, and 4 correlated significantly with the magnitude of the IAP change (r = 0.45, p < 0.05). CONCLUSION: The IAP rise during isometric quadriceps contraction is a feature of all patients with an inflammatory based effusion irrespective of the duration of the effusion. This is not the case in patients with an ATE. In inflammatory synovitis the rise in intra-articular pressure with isometric quadriceps contraction relates to effusion volume. It is concluded that the inflammatory process prevents reflex muscle inhibition, a locally protective mechanism that minimises the potential for intermittent ischaemia/oxidative injury.

Worsening of pica as a symptom of depressive illness in a person with severe mental handicap.

The case of a person with severe mental handicap whose pica became uncontrollable during episodes of depressive illness is described. Treatment of the depression with lofepramine markedly reduced the pica, and withdrawal of lofepramine led to recurrence. It is suggested that biological symptoms of depression should be monitored in people with severe mental handicap who show significant episodic worsening of long-standing repetitive behaviour.

Elderly people with learning disabilities in hospital: a psychiatric study.

In a study of 124 hospital residents with a learning disability aged 60 years and over, DSM-III-R diagnostic criteria were used to determine the prevalence of dementia (12.9%), mood disorder (8.9%) and schizophrenia (6.5%). The figure for dementia confirms the prevalence given in previous studies, but the figures for mood disorder and schizophrenia are higher. It was found that mood disorder was commoner in the age group 60-69 years (P > 0.01) and dementia was commoner in the age group 70-79 years (P > 0.01). There were no significant differences in the prevalence of schizophrenia with age.