TETANUS—Prophylaxis and Treatment of the Disease

Cleansing and debridement is paramount in dealing with tetanus-prone wounds (severe crushing injuries, piercing wounds, blisters and burns are outstanding examples, particularly if contaminated with dirt, grass or other debris).Prophylaxis then is relatively easy in persons who have been actively immunized by toxoid injections. For them, a “booster” injection is indicated.Use of antitoxin, however, is hazardous, whether for prophylaxis or for treatment of the disease. Since it may in itself cause severe disease, including anaphylactic reaction and serum sickness, decision to use it must be weighed against the possibility of the development of tetanus in each case.To prepare for use of it, careful history should be taken, with particular reference to sensitivity to horse dander. Dermal tests, and perhaps ophthalmic tests, for sensitivity to the serum should be carried out. Even the tests may be hazardous and precautions should be taken accordingly.If it is decided that the use of antitoxin is necessary even though the patient is sensitive to the material, desensitization must be carried out promptly, with adequate preparation for severe reaction.There is experimental evidence that antibiotics of the tetracycline group, given soon after injury, may have prophylactic effect against tetanus.     

Development of the Partner’s Treatment of Animals Scale

Although studies of the relationship between animal abuse and intimate partner violence have proliferated in recent years, building upon previous work and making cross-study comparisons have been rendered difficult by the utilization of differing operationalizations of animal maltreatment within this literature. This paper aims to mitigate this problem by introducing and detailing a scale of animal maltreatment by romantic partners, developed and tested with a sample of 55 women in domestic violence shelters who self-identified as victims of intimate partner violence. The Partner’s Treatment of Animals Scale (PTAS) is comprised of five scales (emotional animal abuse, threats to harm animals, animal neglect, physical animal abuse, and severe physical animal abuse) that have strong demonstrated reliability. The construction of the scales is presented in this paper, and recommendations are made for employing the PTAS in subsequent studies.     

Benefits of Iron Chelators in the Treatment of Parkinson’s Disease

As a novel discovered regulated cell death pattern, ferroptosis has been associated with the development of Parkinson’s disease (PD) and has attracted widespread attention. Nevertheless, the relationship between ferroptosis and PD pathogenesis is still unclear. This study aims to investigate the effect of iron overload on dopaminergic (DA) neurons and its correlation with ferroptosis. Here we use nerve growth factor (NGF) induced PC12 cells which are derived from pheochromocytoma of the rat adrenal to establish a classical PD in vitro model. We found significantly decreased cell viability in NGF-PC12 cell under ammonium ferric citrate (FAC) administration. Moreover, excessive intracellular iron ions induced the increase of (reactive oxygen species) ROS release as well as the decrease of mitochondrial membrane potential in PC12-NGF cells. In addition, we also found that overloaded iron can activate cell apoptosis and ferroptosis pathways, which led to cell death. Furthermore, MPP-induced PD cells were characterized by mitochondrial shrinkage, decreased expression of glutathione peroxidase 4 (Gpx4) and ferritin heavy chain (FTH1), and increased divalent metal transporter (DMT1) and transferrin receptor 1 (TfR1) expression level. In contrast, Lip-1 and DFO increased the expression level of GPX4 and FTH1 compared to MPP-induced PD cell. In conclusion, we indicated that overloaded intracellular iron contributes to neurons death via apoptosis and ferroptosis pathways, while DFO, an iron chelator, can inhibit ferroptosis in order to protect the neurons in vitro.

     

Effects of Olanzapine–Fluoxetine Combination Treatment of Major Depressive Disorders on the Quality of Life During Acute Treatment Period

The objective of the study was to explore the effects of olanzapine–fluoxetine combination (OFC) treatment of major depressive disorders on the quality of life in the acute treatment period. Methods were prospective and observational design. One hundred and three patients of major depressive disorders were observed. One group of 53 patients received OFC treatment (OFC group); the other group of 50 patients received the treatment of duloxetine (duloxetine group). Two groups were needed to be observed 8 weeks. Observed indicators were Hamilton Depression Rating Scale for Depression (HAMD-24) and four factor scores: the slow, sleep disorders, anxiety/somatization, and hopelessness, Clinical Global Impression-Severity of Illness (CGI-S), WHO quality of life scale (WHOQOL-BREF), and sub-rate measurements. HAMD-24 and four factor scores observation time were assessed before and after treatment; 1, 2, 4, 8 weeks, WHOQOL-BREF score, and sub-time measurements were assessed before treatment and 8 weeks after treatment. HAMD-24 scores of OFC patients in the first week were significantly lower than those of the duloxetine group. The sleep factor scores of OFC patients were significantly lower than those of the duloxetine group in 4 and 8 weeks. By the end of 8 weeks, OFC group was rated significantly lower than the duloxetine group in the physical area. In the acute treatment period, OFC treatment effected faster than the single duloxetine in patients with major depressive disorders. OFC effected within 1 week and was better than the single duloxetine in improving the sleep and physical conditions.     

Computational Investigation of Pkcβ Inhibitors for the Treatment of Diabetic Retinopathy

Diabetic Retinopathy (DR) is one of the attenuating complications of diabetes mellitus. The key gene responsible for causing diabetic retinopathy is protein kinase C beta (PKCβ). Protein kinase C is a family of protein kinase enzymes which are involved in controlling the function of other proteins through phosphorylation mechanism and plays a crucial role in signal transduction mechanisms. Among all the PKC isoenzymes, PKCβ could be a significant isoenzyme involved in vascular dysfunction during hyperglycemia. Studies show that oral administration of PKCβ inhibitor Ruboxistaurin ({"type":"entrez-nucleotide","attrs":{"text":"LY333531","term_id":"1257370768","term_text":"LY333531"}}LY333531), decreases vessel permeability and improves retinal condition. Thus compounds that decrease the PKCβ activation would be helpful in the treatment of diabetic retinopathy. The compounds similar to Ruboxistaurin are taken from Super Target database and docking analysis was performed. Maleimide derivative 3 showed highest binding affinities compared to Ruboxistaurin and so we advise that compound may be utilized in the treatment of diabetic retinopathy.     

Etanercept in the Treatment of Intestinal Behcet’s Disease

Behcet’s disease (BD) accompanied by intestinal involvement is called intestinal BD. Although recent studies have attained positive feedback with the administration of anti-TNF-α agents in patients with BD, only a few reports on the study of etanercept in intestinal BD have been found. In this study, 35 cases of intestinal BD were treated with conventional therapy (prednisone or methotrexate) for a minimum period of 3 months (group 1). Another 19 patients who failed to respond to conventional therapy were then treated with etanercept (25 mg twice a week for 3 months). During each subsequent relapse, the patients were given the same treatment. The main outcome measures were the four criteria for diagnosis of BD (buccal ulcers, genital ulcers, ocular lesions, and skin lesions), the manifestation of intestinal involvement (abdominal symptoms, double-balloon enteroscopy), laboratory examinations of the acute phase reactants (erythrocyte sedimentation rate) and C-reactive protein, and relapses. As a result of the administered therapy, the healing rate of buccal and genital ulcers, the remission rate of ocular lesions, skin lesions, and abdominal symptoms, the healing rate of intestinal ulcers, and the recovery rate of ESR and CRP were significantly higher in group 2 than those of group 1. The relapse rate in the etanercept therapy was reduced significantly when compared with conventional therapy group. In conclusion, etanercept treatment, in contrast to the conventional therapy, can result in better curative effect and less adverse reactions in intestinal BD.     

A Pill for the Ill? Patients’ Reports of Their Experience of the Medical Encounter in the Treatment of Depression

Background

Starting in the 1960s, a broad-based patients’ rights movement began to question doctors’ paternalism and to demand disclosure of medical information, informed consent, and active participation by the individual in personal health care. According to scholars, these changes contributed to downplay the biomedical approach in favor of a more patient-oriented perspective. The Swedish non-profit organization Consumer Association for Medicines and Health (KILEN) has offered the possibility for consumers to report their perceptions and experiences from their use of medicines in order to strengthen consumer rights within the health care sector.

Methodology

In this paper, qualitative content analysis was used to analyze 181 KILEN consumer reports of adverse events from antidepressant medications in order to explore patients’ views of mental ill health symptoms and the doctor-patient interaction.

Principal Findings

Overall, the KILEN stories contained negative experiences of the patients’ medical encounters. Some reports indicated intense emotional outrage and strong feelings of abuse by the health care system. Many reports suggested that doctors and patients had very different accounts of the nature of the problems for which the patient was seeking help. Although patients sought help for problems like tiredness and sleeplessness (often with a personal crisis of some sort as a described cause), the treating doctor in most cases was exceptionally quick in both diagnosing depression and prescribing antidepressant treatment. When patients felt they were not being listened to, trust in the doctor was compromised. This was evident in the cases when the doctor tried to convince them to take part in medical treatment, sometimes by threatening to withdraw their sick-listing.

Conclusions

Overall, this study suggests that the dynamics happening in the medical encounter may still be highly affected by a medical dominance, instead of a patient-oriented perspective. This may contribute to a questionable medicalization and/or pharmaceuticalization of depression.     

The Role of External Irradiation in the Treatment of Transitional Cell Carcinoma of the Bladder—A Review of Fifty Cases

Of 100 patients with carcinoma of the bladder seen in the Section of Therapeutic Radiology, University of California, San Francisco, between 1957 and 1962, 59 were accepted for radiation treatment. Fifty had transitional cell carcinoma and were treated with supervolt therapy (1 mev or cobalt-60).Two types of tumors were again found suitable for external irradiation: Papillary carcinomas Grades II and III, as long as they have not, or at least have not massively, invaded muscle; and undifferentiated carcinomas, Grade IV, regardless of degree of extension through the pelvis. The former type, if single, is treated by irradiation for the first recurrence after one attempt with radical transurethral resection. In the presence of multiple lesions at the first examination, radiation therapy is given immediately. The latter type is treated by radiation therapy without any attempt at surgical removal.Of 37 patients, Stages A to C, treated more than three years ago, 14 (38 per cent) lived more than three years and eight (22 per cent) had no cystoscopic or clinical signs of active disease and had normal bladder function. Of 23 patients treated more than five years ago, eight were alive after five years (35 per cent) and four (17 per cent) remained controlled by radiation therapy alone, with normal bladder function.No major complications were observed. In particular, no fibrosis of the bladder occurred. Doses ranged from 5,000 r in five and a half weeks to 6,000 r in seven weeks.A close cooperation between urologic surgeons and radiotherapists during recent years permits long-range treatment planning from the time of diagnosis, which is essential in the effective therapy of carcinoma of the bladder.     

Isolation of α and β Brain Tubulin Subunits after Alkaline Treatment of the Protein

We demonstrate here that brain purified tubulin can be dissociated into and subunits at pH > 10 and that the subunits can be separated by using the Triton X-114 phase separation system. After phase partition at pH > 10, tubulin but not tubulin behaves as a hydrophobic compound appearing in the detergent rich phase. After three extractions of the alkaline aqueous phase with Triton X-114, about 90% of the tubulin was recovered in the detergent rich phase. The hydrophobic behavior observed for tubulin after its dissociation at pH 11.5 was not due to an irreversible change of the protein, because when the detergent rich phase containing tubulin was diluted with a buffer solution at pH 7.3 and the solution allowed to partition again, -tubulin is recovered in the aqueous phase. The detergent in the aqueous phase of the and tubulin preparations can be removed up to 90% by 12 h dialysis. The and subunits of tubulin from kidney and liver behave, in this phase separation system, like those of brain tubulin.     

Intra-Peritoneal Hyperthermia Combining α-Galactosylceramide in the Treatment of Ovarian Cancer

The purpose of this study was to investigate the anti-tumor effect and potential mechanisms of i.p. hyperthermia in combination with α-galactosylceramide (α-GalCer) for the treatment of ovarian cancer. In this study, immuno-competent tumor models were established using murine ovarian cancer cell lines and treated with i.p. hyperthermia combining α-GalCer. Th1/Th2 cytokine expression profiles in the serum, NK cell cytotoxicity and phagocytic activities of dendritic cells (DCs) were assayed. We also analyzed the number of CD8⁺/IFN-γ⁺ tumor specific cytotoxic T cells, as well as the tumor growth based on depletion of lymphocyte sub-population. Therapeutic effect on those ovarian tumors was monitored by a non-invasive luminescent imaging system. Intra-peritoneal hyperthermia induced significant pro-inflammatory cytokines expression, and sustained the response of NK and DCs induced by α-GalCer treatment. The combination treatment enhanced the cytotoxic T lymphocyte (CTL) immune response in two mouse ovarian cancer models. This novel treatment modality by combination of hyperthermia and glycolipid provides a pronounced anti-tumor immune response and better survival. In conclusion, intra-peritoneal hyperthermia enhanced the pro-inflammatory cytokine secretion and phagocytic activity of DCs stimulated by α-GalCer. The subsequent CTL immune response induced by α-GalCer was further strengthened by combining with i.p. hyperthermia. Both innate and adaptive immunities were involved and resulted in a superior therapeutic effect in treating the ovarian cancer.     

Targeting Estrogen Receptors for the Treatment of Alzheimer’s Disease

The significantly higher incidence of Alzheimer's disease (AD) in women than in men has been attributed to loss of estrogen and a variety of related mechanisms at the molecular, cellular, and hormonal levels, which subsequently elucidate neuroprotective roles of estrogen against AD-related pathology. Recent studies have proposed that beneficial effects of estrogen on AD are directly linked to its ability to reduce amyloid-β peptides and tau aggregates, two hallmark lesions of AD. Despite high expectations, large clinical trials with postmenopausal women indicated that the beneficial effects of estrogen therapies were insignificant and, in fact, elicited adverse effects. Here, we review the current status of AD prevention and treatment using estrogens focusing on recent understandings of their biochemical links to AD pathophysiology. This review also discusses development of selective ligands that specifically target either estrogen receptor α (ERα) or ERβ isoforms, which are potentially promising strategies for safe and efficient treatment of AD.     

Synthesis and Characterization of Polysialic Acid–Uricase Conjugates for the Treatment of Hyperuricemia

Uricase, an enzyme used for the treatment of hyperuricemia, is conjugated with polysialic acid (PSA) of average molecular weight of 10 kDa by reductive amination in presence of NaCNBH3 in order to improve its pharmacological properties. Polysialylation with 50-,100-,150- and 200-fold molar excess of PSA increased the percentage substitution of the free amino groups on enzyme surface (46, 66, 78 and 80 % respectively). The SDS-PAGE is used to visualize the conjugates with increased molecular weight and it retained almost 65 % of their initial specific activity after conjugation. The stability studies at physiological condition reveals improved stability and activity than the native enzyme. The apparent KM of the enzyme has increased slightly from 4.18 × 10^?5 M to 5.46 × 10^?5 M suggesting that the affinity of the substrate to the enzyme has not been altered to a higher extent. The conjugates, when probed against anti-uricase antibodies generated in rabbit, showed a clean decline in the affinity by 35 % and also have retained double the catalytic activity than that of the native enzyme after exposure to antiserum. The results suggest that uricase-PSA conjugates can be used as an alternative to the conventional synthetic polymer-enzyme conjugates.