Fluoride poisoning and the effect on collagen biosynthesis of osseus and non-osseus tissues of rabbit

Fluoride poisoning Is known to cause a debilitating condition clinically referred to as Fluorlsls. The present Investigation on the experimental animal model has been carried out to collect Information on the precise nature of fluoride action, with special reference to collagen biosynthesis. Rabbits subjected to Fluoride poisoning for varying time Intervals were administered with carbon labelled proline. Both osseus and non-osseus tissues were analyzed to measure the rate of Incorporation of labelled proline, and Index for collagen biosynthesis. Part I of the article is dealing with 14C proline uptake by Hydrolyzed collagen (obtained by centrifugation at 5000 × g) and residual protein of tissues viz: Bone, Tendon, Muscle, Kidney cortex, Skin, Lung, Pinna and Trachea. Part II of the article Is dealing with 14C proline uptake by different fraction of collagen Viz: collagenase digested fraction and separated by centrifugation at 9000 × g ; native collagen fibril, acid soluble collagen, alkali soluble collagen and non-collagenous protein. The results obtained In Part I, suggest that In Fluoride poisoning collagen biosynthesis has been greatly impaired both In osseus and non-ossues tissues. This has been further confirmed by the results obtained in Part II of the investigation

Clinicopathological representation of nonmetastatic Ewing sarcoma of the scapula - a case study

Ewing sarcoma (ES) is a rare type of small cell tumor of the bone and soft tissues. About 50% of ES arise in the femur and pelvis. We present a case of ES of the scapula in a seven year old female child. Because of its similarity with other small cell tumors, the diagnosis of ES is challenging and requires a combination of methods like CT scan, MRI report, histopathological evaluation and IHC, etc. The MRI report of our case has shown a consistent 5×4 cm3 mass on the left scapula. Bone marrow aspiration and biopsy of the tumor has been further analyzed. Small, round and oval cells with densely packed nuclei and scanty cytoplasm, which are characteristic to ES were observed microscopically. A positive reaction to vimentin and CD99 and negative result for the biomarkers meant for other types of tumors, favours the diagnosis of ES. The chromosomes analyzed from the peripheral blood of the patient have shown a normal karyotype. Early diagnosis of ES is very crucial for treatment. Histopathology and IHC are indispensible tools in the diagnosis of ES

Structural aberrations in fluorosed human teeth: Biochemical and scanning electron microscopic studies

The present investigation was carried out to provide biochemical and ultrastructural evidences on the aberrations that appear in teeth in human Dental Fluorosis (DF), a condition caused by excess intake of fluoride. Human fluorosed teeth were obtained from the OPD of Madras Dental College, Chennai. Normal tooth samples were also collected from patients who opted for denture. The samples were investigated for fluoride and calcium contents, besides the tooth surfaces were examined under scanning electron microscope to assess the morphological aberrations. An increase in fluoride content and decrease in calcium content in fluorosed human teeth were observed when compared to the control. The scanning electron micrographs of the enamel surface of fluorosed human teeth show pitted, uneven and rough surfaces. Cracks and fissures were also observed on the enamel surface of fluorosed teeth. The present study provides evidence to suggest that pitting, perforation and structural alterations in DF are the result of impaired enamel mineralization

“How can our children learn from us about our way of life or understand who they are?”:Residential schools and their impact on the wellbeing of Indigenous youth in Attapadi, South India

Residential schools are commonly used in India to provide education for Indigenous youth, which requires young people to stay for long periods at distance from their families and communities. Internationally, there is clear evidence for the deleterious effects of residential schools on the mental health and social and community outcomes of Indigenous children, however little is known about the Indian Indigenous experience. This study examined the impact of residential schooling on Indigenous children's wellbeing and that of their communities, using data from an ethnographic research project in Attapadi, Kerala, including interviews, focus group discussions and participant observation with Indigenous communities. Key outcomes from residential schooling reported by the participants include the fear of losing Indigenous identity, shame of being Indigenous, change in the attitude of young people when they returned from schools, and feelings of confusion and stress that young Indigenous participants felt trying to fit into their communities on their return. Findings suggest that these Indigenous youth felt disconnected from several factors that are known to promote resilience for Indigenous communities including a strong cultural identity, connection to the land and ancestors, thereby making them more vulnerable to poor mental health and negative impacts on their overall wellbeing. Addressing these concerns requires a detailed understanding of the specific factors influencing outcomes for Indigenous youth within the Indian residential schooling system, and designing and implementing data-informed conceptual, structural and policy change including the provision of culturally safe mental health services.</p

Effective interventional approach to control anaemia in pregnant women

Anaemia in pregnancy and low birth weight babies, a serious public health problem, troubles India and several other nations. This article reports the results of a approach to address the issue. Women up to 20 week pregnancy with haemoglobin (Hb) 9.0 g/dl or less, those with urinary fluoride beyond 1.0 mg/l and not suffering from any other ailments, were selected. Out of the 205 pregnant women attending antenatal clinics (ANCs) during 1st and 2nd trimesters, the sample and control groups were selected through computerized random sampling procedure. Ninety pregnant women formed the sample group and 115 formed the control group. The sample group was introduced to two interventions, viz.: (1) removal of fluoride from ingestion through drinking water, food and other sources, (2) counselling based intake of essential nutrients, viz. calcium, iron, folic acid, vitamins C, E and other antioxidants through dairy products, vegetables and fruits. No intervention was introduced for the control group. Sample and control groups were monitored for urinary fluoride and Hb until delivery during their visits to ANC. Birth weight of the babies were recorded from the labour room register. Results reveal that (1) the urine fluoride levels decreased in 67% and 53% of the pregnant women respectively, who attended ANCs during 1st and 2nd trimester of pregnancy. (2) An increase in Hb upon withdrawal of fluoride followed by nutritional intervention in 73% and 83% respectively has also been recorded. (3) Body mass index (BMI) also enhanced. (4) The percentage of pre-term deliveries was decreased in sample group compared to control. (5) Birth weight of babies enhanced in 80% and 77% in sample group women who attended ANC in 1st and 2nd trimester respectively as opposed to 49% and 47% respectively in the control group. (6) The number of low birth weight babies was reduced to 20% and 23% respectively in sample as opposed to 51% and 53% in control groups

Percutaneous Intervention or Bypass Graft for Left Main Coronary Artery Disease? A Systematic Review and Meta-Analysis

Background. The safety and efficacy of percutaneous coronary intervention (PCI) versus coronary artery bypass grafting (CABG) for stable left main coronary artery disease (LMCAD) remains controversial.Methods. Digital databases were searched to compare the major adverse cardiovascular and cerebrovascular events (MACCE) and its components. A random effect model was used to compute an unadjusted odds ratio (OR).Results. A total of 43 studies (37 observational and 6 RCTs) consisting of 29,187 patients (PCI 13,709 and CABG 15,478) were identified. The 30-day rate of MACCE (OR, 0.56; 95% CI, 0.42-0.76;p = 0.0002) and all-cause mortality (OR, 0.52; 95% CI, 0.30-0.91;p = 0.02) was significantly lower in the PCI group. There was no significant difference in the rate of myocardial infarction (MI) (p = 0.17) and revascularization (p = 0.12). At 5 years, CABG was favored due to a significantly lower rate of MACCE (OR, 1.67; 95% CI, 1.18-2.36;p = <0.04), MI (OR, 1.67; 95% CI, 1.35-2.06;p = <0.00001), and revascularization (OR, 2.80; 95% CI, 2.18-3.60;p = <0.00001), respectively. PCI was associated with a lower overall rate of a stroke, while the risk of all-cause mortality was not significantly different between the two groups at 1- (p = 0.75), 5- (p = 0.72), and 10-years (p = 0.20). The Kaplan-Meier curve reconstruction revealed substantial variations over time; the 5-year incidence of MACCE was 38% with CABG, significantly lower than 45% with PCI (p = <0.00001).Conclusion. PCI might offer early safety advantages, while CABG provides greater durability in terms of lower long-term risk of ischemic events. There appears to be an equivalent risk for all-cause mortality

Envisioning Yoga Therapy as A Stride towards Successful Ageing

Geriatric Social Work is becoming ostensibly crucial in contemporary times. The modes and modalities being discussed in strengthening geriatric well-being deserve mammoth attention. In this context, Yoga Therapy is being envisioned as one among the strides towards Successful Ageing. The practice of Yoga in India can be traced to thousands of years back and has rolled down to generations through innumerable strategies. Yoga is considered as a practical philosophy that facilitates people to improve their Quality of Life. It is a discipline that has evolved in response to the problems in contemporary society without losing its true essence. Research in the field of Yoga Therapy advocates it to be the best means to ensure the quality living, especially in old age. Yoga helps to mitigate, alleviate, and reverse many of the geriatric problems, both physical and mental. The proposed paper is based on an experimental study conducted among elderly people in Kerala. The paper describes Yoga in its essence based on Patanjaly Yoga Sutra thereby scientifically analyzing its effect on our body. It emphasizes the practicality for quality living in old age and provides suggestions for successful ageing.

Macrophage Pro-Inflammatory Response to Francisella novicida Infection Is Regulated by SHIP

Francisella tularensis, a Gram-negative facultative intracellular pathogen infecting principally macrophages and monocytes, is the etiological agent of tularemia. Macrophage responses to F. tularensis infection include the production of pro-inflammatory cytokines such as interleukin (IL)-12, which is critical for immunity against infection. Molecular mechanisms regulating production of these inflammatory mediators are poorly understood. Herein we report that the SH2 domain-containing inositol phosphatase (SHIP) is phosphorylated upon infection of primary murine macrophages with the genetically related F. novicida, and negatively regulates F. novicida–induced cytokine production. Analyses of the molecular details revealed that in addition to activating the MAP kinases, F. novicida infection also activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in these cells. Interestingly, SHIP-deficient macrophages displayed enhanced Akt activation upon F. novicida infection, suggesting elevated PI3K-dependent activation pathways in absence of SHIP. Inhibition of PI3K/Akt resulted in suppression of F. novicida–induced cytokine production through the inhibition of NFκB. Consistently, macrophages lacking SHIP displayed enhanced NFκB-driven gene transcription, whereas overexpression of SHIP led to decreased NFκB activation. Thus, we propose that SHIP negatively regulates F. novicida–induced inflammatory cytokine response by antagonizing the PI3K/Akt pathway and suppressing NFκB-mediated gene transcription. A detailed analysis of phosphoinositide signaling may provide valuable clues for better understanding the pathogenesis of tularemia

Molecular Mechanisms of Bortezomib Resistant Adenocarcinoma Cells

Bortezomib (Velcade™) is a reversible proteasome inhibitor that is approved for the treatment of multiple myeloma (MM). Despite its demonstrated clinical success, some patients are deprived of treatment due to primary refractoriness or development of resistance during therapy. To investigate the role of the duration of proteasome inhibition in the anti-tumor response of bortezomib, we established clonal isolates of HT-29 adenocarcinoma cells adapted to continuous exposure of bortezomib. These cells were ∼30-fold resistant to bortezomib. Two novel and distinct mutations in the β5 subunit, Cys63Phe, located distal to the binding site in a helix critical for drug binding, and Arg24Cys, found in the propeptide region were found in all resistant clones. The latter mutation is a natural variant found to be elevated in frequency in patients with MM. Proteasome activity and levels of both the constitutive and immunoproteasome were increased in resistant cells, which correlated to an increase in subunit gene expression. These changes correlated with a more rapid recovery of proteasome activity following brief exposure to bortezomib. Increased recovery rate was not due to increased proteasome turnover as similar findings were seen in cells co-treated with cycloheximide. When we exposed resistant cells to the irreversible proteasome inhibitor carfilzomib we noted a slower rate of recovery of proteasome activity as compared to bortezomib in both parental and resistant cells. Importantly, carfilzomib maintained its cytotoxic potential in the bortezomib resistant cell lines. Therefore, resistance to bortezomib, can be overcome with irreversible inhibitors, suggesting prolonged proteasome inhibition induces a more potent anti-tumor response

Microarray Analysis of Human Monocytes Infected with Francisella tularensis Identifies New Targets of Host Response Subversion

Francisella tularensis is a gram-negative facultative bacterium that causes the disease tularemia, even upon exposure to low numbers of bacteria. One critical characteristic of Francisella is its ability to dampen or subvert the host immune response. In order to help understand the mechanisms by which this occurs, we performed Affymetrix microarray analysis on transcripts from blood monocytes infected with the virulent Type A Schu S4 strain. Results showed that expression of several host response genes were reduced such as those associated with interferon signaling, Toll-like receptor signaling, autophagy and phagocytosis. When compared to microarrays from monocytes infected with the less virulent F. tularensis subsp. novicida, we found qualitative differences and also a general pattern of quantitatively reduced pro-inflammatory signaling pathway genes in the Schu S4 strain. Notably, the PI3K / Akt1 pathway appeared specifically down-regulated following Schu S4 infection and a concomitantly lower cytokine response was observed. This study identifies several new factors potentially important in host cell subversion by the virulent Type A F. tularensis that may serve as novel targets for drug discovery