Ultrastructural alterations of renal tissue in a male patient with Fabry’s disease

Background: Fabry’s disease is an X-linked lipid storage disorder due to deficient lysosomal alpha galactosidase A.Case Presentation: Kidney biopsy was done on a 19 year old male patient with complaint of acroparesthesia, maculopapular skin lesions and cornea verticillata. Kidney biopsy tissue was processed and examined by electron microscopy. Changes were inclusion bodies in the cytoplasm of the renal cells. These inclusions were osmophilic with concentric lamellation of clear and dark layers, showing onion skin appearance. The podocytes were mostly affected and some of the foot processes were fused. Cross-sections of collagen fibers were also evident, indicating fibrosis.Conclusion: The ultra-structure of the kidney clearly showed the intra-cytoplasmic glycosphingolipid accumulation in renal cells, responsible for progressive decline in renal function which could lead to kidney failure. The final diagnosis of Fabry’s disease was confirmed. In the present case-study, electron microscopy proved to be a valuable diagnostic aid.Keywords: Fabry’s disease, Male patient, Ultra-structural alteration

Role of the thalamic parafascicular nucleus cholinergic system in the modulation of acute corneal nociception in rats

The present study investigated the effects of microinjections of acetylcholine (a cholinergic agonist), physostigmine (a cholinesterase inhibitor), atropine (an antagonist of muscarinic cholinergic receptors) and hexamethonium (an antagonist of nicotinic cholinergic receptors) into the parafascicular nucleus of thalamus on the acute corneal nociception in rats. Acute corneal nociception was induced by putting a drop of 5 M NaCl solution onto the corneal surface of the eye and the number of eye wipes was counted during the first 30s. Both acetylcholine and physostigmine at the same doses of 0.5, 1 and 2 μg significantly (P < 0.05) reduced the number of eye wipes. The intensity of corneal nociception was not changed when atropine and hexamethonium were used alone. Atropine (4 μg), but not hexamethonium (4 μg) significantly (P < 0.05) prevented acetylcholine (2 μg)- and physostigmine (2 μg)-induced antinociceptive effects. The results indicated that at the level of the parafascicular nucleus of thalamus, the muscarinic cholinergic receptors might be involved in the antinociceptive effects of acetylcholine and physostigmine

The effects of bone marrow-derived mesenchymal stem cells on ovalbumin-induced allergic asthma and cytokine responses in mice

Objective(s): Allergic Asthma is an inflammatory disease of the lungs that is characterized by increased infiltration of leukocytes into the airways, limiting the respiratory function. Studies suggest that a defective general regulatory system against inflammation could be a significant factor in allergic asthma. It has been shown that Mesenchymal stem cells (MSCs) have a cellular immunosuppressive therapeutic potential for inflammatory disorders. We investigated whether administration of MSCs during allergen challenge would affect the underlying mechanisms in allergic airways inflammation. Materials and Methods: Fifty mice were used in five control and experimental groups; the experimental mice sensitized by intraperitoneal injection of OVA and aluminum hydroxide emulsion on days 0, 7, and 14, were then challenged intranasally with OVA or sterile PBS on days 14, 25, 26, and 27. Before allergen challenge on day 14, experimental mice received tail vein injection of MSCs in PBS, whereas control mice received PBS alone. Cytokine and IgE analyses were carried out using lung washes as well as serum samples.Results: Our, results showed that MSCs significantly reduced total cells and eosinophilia and serum OVA-specific IgE concentration in OVA-sensitized and challenged mice. Also, results showed that MSCs markedly inhibited expressions of Th2 and Th17 cytokines and elevated levels of Treg cytokines. Conclusion: we found that administration of MSCs could be used as a potential therapeutic approach for allergic asthma

Healing of excisional wound in alloxan induced diabetic sheep: A planimetric and histopathologic study

Healing of skin wound is a multi-factorial and complex process. Proper treatment of diabetic wounds is still a major clinical challenge. Although diabetes mellitus can occur in ruminants, healing of wounds in diabetic ruminants has not yet been investigated. The aim of this study was to evaluate healing of ovine excisional diabetic wound model. Eight 4-month-old Iranian Makoui wethers were equally divided to diabetic and nondiabetic groups. Alloxan monohydrate (60 mg kg-1, IV) was used for diabetes induction. In each wether, an excisional wound was created on the dorsum of the animal. Photographs were taken in distinct times for planimetric evaluation. Wound samples were taken on day 21 post-wounding for histopathologic evaluations of epidermal thickness, number of fibroblasts and number of new blood vessels. The planimetric study showed slightly delay in wound closure of diabetic animals, however, it was not significantly different from nondiabetic wounds (p ≥ 0.05). Furthermore, epidermal thickness, number of fibroblasts and number of blood vessels were significantly lower in diabetic group (p < 0.05). We concluded that healing of excisional diabetic wounds in sheep may be compromised, as seen in other species. However, contraction rate of these wounds may not be delayed due to metabolic features of ruminants and these animals might go under surgeries without any serious concern. However, healing quality of these wounds may be lower than normal wounds

Healthy Male Individuals Possess Higher Plasma HER-2 Level than Females

Considering HER2 as one of the well-known biomarkers in the cancer field, and published articles regarding serumlevels of HER2, in this paper we tried to highlight the issue that most studies don’t stratify the HER-2 concentrationof individuals in terms of gender. In this brief survey, healthy individuals with no prior non-communicable diseaseswere categorized as males (n=34) and females (n=43), and all samples were evaluated for plasma HER-2 levelsat once. Surprisingly, the plasma level of HER-2 of healthy male individuals (mean= 2.28 ± 0.21 ng/mL) wassignificantly (P<0.0001) higher than the plasma level of HER-2 of healthy females (mean: 0.06 ± 0.09 ng/mL),with no overlap. Therefore, we suggest that more studies are required to re-check the cutoff values for HER-2plasma levels based on gender since the clinical implications of a unique HER-2 cutoff for both genders may beseriously concerning

The global burden of cancer attributable to risk factors, 2010-19 : a systematic analysis for the Global Burden of Disease Study 2019

Background Understanding the magnitude of cancer burden attributable to potentially modifiable risk factors is crucial for development of effective prevention and mitigation strategies. We analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019 to inform cancer control planning efforts globally. Methods The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented. Findings Globally, in 2019, the risk factors included in this analysis accounted for 4.45 million (95% uncertainty interval 4.01-4.94) deaths and 105 million (95.0-116) DALYs for both sexes combined, representing 44.4% (41.3-48.4) of all cancer deaths and 42.0% (39.1-45.6) of all DALYs. There were 2.88 million (2.60-3.18) risk-attributable cancer deaths in males (50.6% [47.8-54.1] of all male cancer deaths) and 1.58 million (1.36-1.84) risk-attributable cancer deaths in females (36.3% [32.5-41.3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20.4% (12.6-28.4) and DALYs by 16.8% (8.8-25.0), with the greatest percentage increase in metabolic risks (34.7% [27.9-42.8] and 33.3% [25.8-42.0]). Interpretation The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Crocin Enhanced Functional Recovery after Sciatic Nerve Crush Injury in Rats

Objective(s): Crocin is a constituent of saffron and has many biological functions. The present study aimed to investigate the effects of intraperitoneal (IP) injection of crocin on sciatic nerve regeneration in male Wistar rats. Materials and Methods: Fifty-four rats were divided into 9 groups: groups 1-4 (intact + normal saline and intact + crocin at doses of 5, 20 and 80 mg/kg, respectively); group 5 (sham surgery + normal saline); groups 6-9 (crush + normal saline and crush + crocin at doses of 5, 20 and 80 mg/kg, respectively). Normal saline and crocin were IP injected for 10 consecutive days after induction of a standard crush injury in left sciatic nerve. Footprints were obtained 1 day before and weekly after induction of nerve injury for evaluation of sciatic functional index (SFI). Blood samples were taken for evaluation of malondialdehyde (MDA) levels. Histopathological changes of sciatic nerve were investigated by light microscopy. Results: Sciatic nerve crush-injured rats showed SFI values reduction, increased plasma MDA levels and produced Wallerian degeneration in sciatic nerve. Crocin at a dose of 5 mg/kg had no significant effects. At doses of 20 and 80 mg/kg, crocin accelerated the SFI recovery, decreased MDA levels and reduced Wallerian degeneration severity. Conclusion: The present study suggests that the neuroprotective effects afforded by crocin may be due in part to reduction of free radicals-induced toxic effects

Effects of Histidine and Dexamethasone on the Local Inflammation Induced by Histamine in Rats

In this study, the effects of separate and combined intraperitoneal (IP) injections of histidine and dexamethasone were investigated on local inflammation in rats. Local inflammation was induced by subcutaneous (SC) injection of histamine (100 μl, 0.1%) in ventral surface of right hind paw. The thickness of paw was measured at 30 min before and 30, 60, 90, 120, 150 and 180 min after injection of histamine, using a fine caliper. The number of neutrophils in paw tissue sections was counted 3 h after intraplantar (IPL) injection of histamine. The IPL injected histamine elicited an inflammatory response that was characterized by increase of paw thickness and by infiltration of neutrophils in paw tissues. IP injections of histidine at doses of 200 and 400 mg kg-1 and dexamethasone at a dose of 1 mg kg-1 significantly (P < 0.05) decreased both paw thickness and infiltration of neutrophils in paw tissues. In combined treatment, IP injection of histidine (200 mg kg-1) with dexamethasone (1 mg kg-1) produced a more documented response in comparison with histidine and dexamethasone used alone. The results suggested that histidine and dexamethasone have anti-inflammatory activities. Histidine potentiated the anti-inflammatory effect of dexamethasone in histamine-induced local inflammation