Expression of HIF-2a in clear-cell renal cell carcinoma independently predicts overall survival.

The purpose of this study is to evaluate the expression and the prognostic role of main factors, involved in the hypoxia pathway, in patients with clear-cell renal cell carcinoma (ccRCC). Immunohistochemical expression of Hypoxia inducible factors (HIF) HIF-1a, HIF-2a, prolyl hydroxylases PHD1, PHD2, PHD3, and factor inhibiting HIF (FIH) was assessed on a tissue microarray, containing tumour and corresponding normal kidney tissue from 66 patients underwent surgery for ccRCC. Expression levels were evaluated in relation to T stage, Fuhrman grade, cancer-specific, and overall survival (OS). Cytoplasmatic expression of HIF-2a was positively correlated with expression of HIF-1a (p = 0.011). HIF-1a expression was also positively correlated with PHD3 and FIH (p = 0.020 and p = 0.039). Expression of HIF-1a was associated with lower Fuhrman grade (p = 0.008), while HIF-2a overexpression with unfavourable grade (p = 0.026). PHD3 was significant downregulated (84.8%). Age, LDH, presence of necrosis, Fuhrman grade, T stage, and HIF-2a cytoplasmatic expression were significant associated with OS of patients in univariable analysis. In multivariable analysis, HIF-2a expression (p = 0.006) and T stage (p = 0.001) remained as the only independent predictors for overall survival. These results indicate that HIF-2a overexpression not only is inversely correlated with Fuhrman grade in ccRCC, but also represents a strong independent prognostic factor for a poor overall survival.

A study about neck pain on active population who visit Primary Health Centers.

BACKGROUND: Cervical pain is very common among population and several methods have been used until now in order to evaluate it. The main aim of this study is to estimate the prevalence of non-specific neck pain and the special features of it through its relation to demographic agents, habits and physiology parameters. Additionally, this study aims to select the most valid and objective methods for neck pain evaluation, which could also be useful in Primary Health Care and could give new prospectives. METHODS: This is a cross sectional study with a sample of 440 people 20-40 years old who visited the Public Centers in the County of Thessaloniki. The sample was chosen randomly. The subjects were separated in two groups (neck pain and no pain group). A questionnaire was distributed to the sample. The devices were an algometer which was used to estimate pain threshold and an electronic hand watch/smartphone which was used to evaluate pulse and skin humidity. RESULTS: The 38.6% of the samples seemed to suffer from neck pain but real neck pain was found only in the 21% of the sample. The disturbance in neck area because of stiffness and fatigue was found in 51% of the subjects and 25.9% of theme felt both pain and fatigue. The factors which were related to neck pain were female sex (p<0.001), age after 40 (p=0.007), marriage status (p=0.042), smocking (p=0.034), lack of physical exercise (p=0.01) and stress (p<0.001). Neck pain was strongly associated to pain pressure thresholds (PPT) (p<0.001). The PPT were lower in the group who suffered from neck pain. The agents which were not statistically associated with neck pain were the hardness of work (p=0,369), computer use (p=0.07), educational level (p=0.274), alcohol consumption (p=0.748), siesta (p=0.913), depression (p=0.086), heart rate (p=0.216) and skin humidity (p=0.141). There was no correlation between NRS and pain thresholds (p=0.947). The majority of people seemed to suffer from mild disability caused by neck pain (56.7%). Almost the half of the sample did not asked for professional help for their neck pain (48%) and seemed to be ignorant about the role of general practitioner at the management of their neck pain (44.1%). CONCLUSION: The examination of the patients showed that neck pain is often confused with stiffness and fatigue at the neck area. The NDI and HADS questionnaires could be easily used to evaluate respectively the disability and the psychological status of a person who suffers from neck pain. Algometry seems to enhance the objectiveness at the field of neck pain evaluation. The algometer showed high validity and reliability as a mean of neck pain evaluation under the condition that it is applied by a health professional with experience on its use. Neck pain is a complexed symptom and should be evaluated from an integrated point of view. These tools could probably be used in Primary Health Care as contemporary resources in the medical practice but more research is needed.

Specific neck pain algometric measurements and their relation to heart rate and skin humidity.

Cervical pain is very common in general population but only few methods have been used to evaluate it with objectiveness. There are only few studies which use algometer as a means of neck pain assessment. Studies have shown that algometer could be used in pain evaluation but more studies are necessary to support this. The main purpose of the study was the evaluation of algometer as a means of an objective measurement of pain threshold to people with non-specific neck pain. The study focused on the search of correlation between neck pain and pain pressure threshold (PPT) after recording the number of the minimum pain feeling in the sample with the pressure of the algometer at specific neck points. The study also aimed at searching the correlation of neck pain with heart rate and skin humidity. This is a part of a cross-sectional study which was held during a PhD study which assessed 185 randomly chosen people, 20-60 years old, who visited all the Public Centers in the County of Thessaloniki. The sample was separated in two groups according to the frequency of their neck pain, those who suffered frequently or almost every day from non-specific neck pain (neck pain group) and those with non-specific neck pain occasionally, rarely or never suffered from it (no pain group). Subjects were randomly chosen from people who visited the Public Centers for any reason. Neck pain was strongly associated with PPT (P<0.001). Heart rate (P=0.216) and skin humidity (P=0.14) were not significantly related to neck pain. According to the results the algometer seems to be a useful tool as a mean of neck pain evaluation and algometry seems to enhance the idea of pain quantification. However more evidence is needed and more studies should be conducted in order to strengthen our results. Latter studies should be designed with more accuracy focusing on details in order to establish algometry as an objective method of pain evaluation.

Chronic massive rotator cuff tear in rats: in vivo evaluation of muscle force and three-dimensional histologic analysis.

BACKGROUND: Massive rotator cuff tear repair is frequently complicated by unsatisfactory clinical results due to possible tendon retraction, muscle atrophy, and fatty degeneration. The objective of this study was the development of a chronic massive tear in a rat model and the evaluation of the muscle force in vivo and of the histologic changes in a 3- dimensional manner. METHODS: To simulate massive rotator cuff tears, both the supraspinatus (SS) and the infraspinatus (IS) tendons were surgically detached from the right humerus of 15 male adult Sprague-Dawley rats. Twelve weeks postoperatively, all animals underwent isometric tension recordings of both the SS and IS muscles. Histologic analysis and image deconvolution processing were performed to estimate the presence and the distribution of atrophy in 3 dimensions. RESULTS: An overall 30% and 35% reduction in muscle force of the SS and IS muscles, respectively, was observed compared with the left uninjured shoulder (P < .005). Histologic analysis revealed that the degeneration and the fatty infiltration were more evident near the tendon and at the dorsal side in both muscle groups. CONCLUSIONS: These results show that functional impairment of SS and IS muscles after chronic massive tendon tears could be attributed to the decrease in muscle force production during their repair on the greater tuberosity and, second, to the comparatively greater degeneration of their dorsal part.

Multitarget molecular hybrids of cinnamic acids.

In an attempt to synthesize potential new multitarget agents, 11 novel hybrids incorporating cinnamic acids and paracetamol, 4-/7-hydroxycoumarin, benzocaine, p-aminophenol and m-aminophenol were synthesized. Three hybrids-2e, 2a, 2g-and 3b were found to be multifunctional agents. The hybrid 2e derived from the phenoxyphenyl cinnamic acid and m-acetamidophenol showed the highest lipoxygenase (LOX) inhibition and analgesic activity (IC50 = 0.34 µΜ and 98.1%, whereas the hybrid 3b of bromobenzyloxycinnamic acid and hymechromone exhibited simultaneously good LOX inhibitory activity (IC50 = 50 µΜ) and the highest anti-proteolytic activity (IC50= 5 µΜ). The hybrid 2a of phenyloxyphenyl acid with paracetamol showed a high analgesic activity (91%) and appears to be a promising agent for treating peripheral nerve injuries. Hybrid 2g which has an ester and an amide bond presents an interesting combination of anti-LOX and anti-proteolytic activity. The esters were found very potent and especially those derived from paracetamol and m-acetamidophenol. The amides follow. Based on 2D-structure-activity relationships it was observed that both steric and electronic parameters play major roles in the activity of these compounds. Molecular docking studies point to the fact that allosteric interactions might govern the LOX-inhibitor binding.

The Effect of Isotretinoin on Insulin Resistance and Serum Adiponectin Levels in Acne Vulgaris Patients: A Systematic Review and Meta-Analysis.

BACKGROUND: Isotretinoin is the drug of choice for severe acne. We sought to examine the potential link between isotretinoin and insulin resistance. METHODS: We conducted a systematic review and meta-analysis in accordance with the PRISMA statement. A comprehensive search of the PubMed/MEDLINE, SCOPUS, and Cochrane databases was performed until 12 January 2022 utilizing the PICO (Patient, Intervention, Comparison, Outcome) tool. Fifteen English-language studies focusing on isotretinoin-treated acne patients were included. Serum levels of insulin, glucose, and adiponectin were evaluated before and after treatment, and insulin sensitivity was assessed using the HOMA-IR. A meta-analysis was conducted using RevMan 5.4.1 software, and a quality assessment was undertaken using the ROBINS-I tool. RESULTS: The meta-analysis unveiled a statistically significant rise in the post-treatment levels of adiponectin, an anti-inflammatory agent, which inhibits liver glucose production while enhancing insulin sensitivity (SMD = 0.86; 95% confidence interval (95% CI) = 0.48-1.25, p-value < 0.0001; I2 = 58%). Our subgroup analysis based on study type yielded consistent findings. However, no statistically significant outcomes were observed for insulin, glucose levels, and the HOMA-IR. CONCLUSIONS: There is not a clear association between isotretinoin and insulin resistance, but it appears to enhance the serum levels of adiponectin, which participates in glucose metabolism.

Cosmeceuticals: A Review of Clinical Studies Claiming to Contain Specific, Well-Characterized Strains of Probiotics or Postbiotics.

The skin serves as a critical barrier against external threats-dehydration, ultraviolet exposure, and infections-playing a significant role in internal homeostasis and moisture retention. Additionally, and equally importantly, it interacts dynamically with the complex microbiome resident in it, which is essential for maintaining skin health. Recent interest has focused on the use of probiotics and postbiotics, besides their ability to modulate the skin microbiome, to enhance barrier function, and exhibit anti-inflammatory properties, to be involved in skincare, by having the potential to improve skin hydration, elasticity, and overall appearance, as well as in reducing signs of aging, such as wrinkles and fine lines. The products-being a combination of a cosmetic regime plus probiotic[s] or postbiotic[s]-are named cosmeceuticals. However, to comply with the regulations for the characterization of a microorganism as a specific probiotic strain, the pro- or postbiotics incorporated into the cosmetic regime should be both genetically and phenotypically defined. Thus, in this review, we present 14 published clinical trials using such cosmetic products with specific, well-characterized strains of probiotics or postbiotics applied to volunteers with healthy skin. Looking at the results of these studies collectively, we can say that these genetically and phenotypically defined strains of either live or inanimate bacteria and/or their components seem to keep the treated skin at least fully hydrated, with intact epithelial tone, increased radiance, and with decreased wrinkle depth, while normalizing the commensal skin microbiota. Future advancements in personalized skin care may lead to genomic sequencing and metabolomics to tailor probiotic and postbiotic treatments to individual skin microbiomes, promising a new frontier in cosmeceuticals.

Three-dimensional morphometric mapping of rat muscle fibers.

INTRODUCTION: Quantitative descriptions of fiber type organization in hind limb muscles are incomplete or rare. METHODS: Fiber morphometrics for both rat tibialis anterior (TA) muscles were measured in 3 dimensions. RESULTS: Slow oxidative fiber area and perimeter varied in all zones. Fast oxidative glycolytic fibers (FOG) were predominant in the mediolateral and posterior zones, and fast glycolytic fibers (FG) predominated in the anterior zone. The mean area of FOG and succinate dehydrogenase intermediate fibers was lowest in the anterior zone. Mean area of FG was highest in the proximal and distal parts of the muscle. The area and perimeter of fast fibers differed significantly between the right and left limbs in the medial zone. In the middle and lateral zones, they differed at the proximal and distal parts. CONCLUSIONS: This detailed analysis in a high resolution, 3-dimensional map provides an essential tool for understanding the structure and function of TA muscles.

Bringing pathology to nanomedicine: a comparison of in vivo toxicity of polymeric nanoparticle carriers with and without chitosan coating.

Over the last years, there has been an increasing number of proposals for the use of nanomaterials in medicine. The safety of novel technologies must be verified, prior to their clinical application. Pathology has much to contribute towards this end. In this study, we compared the in vivo toxicity effects of poly- (lactic-co-glycolic acid) nanoparticles with and without chitosan shell. Both nanoparticle types were loaded with curcumin. The nanoparticles were assessed in vitro for potential cytotoxicity with cell viability studies. For the in vivo test, 36 adult Wistar rats were used, four of which were the control group. The remaining 32 were divided into 2 groups, each of which was administered differentially coated drug carriers: (A) nanoparticles without chitosan coating and (B) nanoparticles with chitosan coating. For both groups, the subcutaneous route was used for administration. Each group was further divided into 2 sub-groups of 8 animals each. The animals of the first sub-groups were sacrificed 24 h after the injection and those of the second on the 7th day. The control group was also divided into 2 subgroups of 2 animals each. At the appointed post-administrative date, the rats were sacrificed, and specimens from the brain, liver, kidneys, heart, stomach, lungs, and from the skin at the injection site were collected and studied histopathologically. The evaluation of both in vitro and in vivo testing shows that nanoparticles with chitosan have significantly less, if any, toxic effects compared to those without chitosan.

Topical prebiotics/postbiotics and PRURISCORE validation in atopic dermatitis. International study of 396 patients.

Aim: To investigate the efficacy and tolerability of a cream (Rilastil Xerolact PB) containing a mixture of prebiotics and postbiotics, and to validate the PRURISCORE itch scale in the management of atopic dermatitis.Methods: The study is based on 396 subjects of both sexes in three age groups (i.e., infants, children, adults) suffering from mild/moderate Atopic Dermatitis, recruited from 8 European countries and followed for 3 months.Results: The product demonstrated good efficacy combined with good/very good tolerability in all age groups. In particular, SCORAD, PRURISCORE and IGA scores decreased significantly over the course of the study. The PRURISCORE was preferred to VAS by the vast majority of patients.Conclusion: Even though the role of prebiotics and postbiotics was not formally demonstrated since these substances were part of a complex formulation, it can be reasonably stated that prebiotics and postbiotics have safety and standardization features that probiotics do not have. In addition they are authorized by regulatory authorities, whereas topical probiotics are not.

Contractile properties and movement behaviour in neonatal rats with axotomy, treated with the NMDA antagonist DAP5.

BACKGROUND: It is well known that axotomy in the neonatal period causes massive loss of motoneurons, which is reflected in the reduction of the number of motor units and the alteration in muscle properties. This type of neuronal death is attributed to the excessive activation of the ionotropic glutamate receptors (glutamate excitotoxicity). In the present study we investigated the effect of the NMDA antagonist DAP5 [D-2-amino-5-phosphonopentanoic acid] in systemic administration, on muscle properties and on behavioural aspects following peripheral nerve injury. METHODS: Wistar rats were subjected to sciatic nerve crush on the second postnatal day. Four experimental groups were included in this study: a) controls (injection of 0.9% NaCl solution) b) crush c) DAP5 treated and d) crush and DAP5 treated. Animals were examined with isometric tension recordings of the fast extensor digitorum longus and the slow soleus muscles, as well as with locomotor tests at four time points, at P14, P21, P28 and adulthood (2 months). RESULTS: 1. Administration of DAP5 alone provoked no apparent adverse effects. 2. In all age groups, animals with crush developed significantly less tension than the controls in both muscles and had a worse performance in locomotor tests (p < 0.01). Crush animals injected with DAP5 were definitely improved as their tension recordings and their locomotor behaviour were significantly improved compared to axotomized ones (p < 0.01). 3. The time course of soleus contraction was not altered by axotomy and the muscle remained slow-contracting in all developmental stages in all experimental groups. EDL, on the other hand, became slower after the crush (p < 0.05). DAP5 administration restored the contraction velocity, even up to the level of control animals 4. Following crush, EDL becomes fatigue resistant after P21 (p < 0.01). Soleus, on the other hand, becomes less fatigue resistant. DAP5 restored the profile in both muscles. CONCLUSIONS: Our results confirm that contractile properties and locomotor behaviour of animals are severely affected by axotomy, with a differential impact on fast contracting muscles. Administration of DAP5 reverses these devastating effects, without any observable side-effects. This agent could possibly show a therapeutic potential in other models of excitotoxic injury as well.

Modulation of nociception and pain-evoked neurobehavioral responses by levetiracetam in a craniotomy pain model.

Traditional and novel analgesic modalities have been extensively tested for post-craniotomy pain management, yet the role of newer antiepileptic drugs in this area remains obscure. This study investigates the impact of levetiracetam (LEV) on pain modulation and neurobehavioral performance in a craniotomy model. Fifty-six Wistar rats were randomly assigned into seven groups: no intervention (CTRL), administration of placebo or LEV with no further intervention (PBO and LEV, respectively), and sham-operation or craniotomy in placebo (PBO-SHAM and PBO-CR, respectively) or LEV-treated rats (LEV-SHAM and LEV-CR, respectively). Pain was assessed by the rat grimace scale before, and at 8 and 24 h after craniotomy, following intraperitoneal injections of LEV (100 mg/kg twice daily) or normal saline two consecutive days before and on the craniotomy day. Elevated plus-maze and olfactory social memory tests were performed at 24- and 48 h post-craniotomy, respectively. Upon testing conclusion blood samples were collected for cytokines estimation. Levetiracetam administration enhanced antinociception in sham and craniotomy groups. In the elevated plus-maze test, LEV-CR rats spent more time in investigating open arms and performed more open arm entries than PBO-SHAM and PBO-CR animals. The olfactory test revealed no between-groups difference in acquisition time during first contact with a juvenile rat, while LEV-CR rats spent less time to recognize the same juvenile rat compared to PBO-SHAM and PBO-CR groups. Furthermore, LEV-treatment attenuated cortisol, interleukin-6 and TNF-a release, in sham and craniotomy animals. In conclusion, preemptive use of LEV decreases nociception, improves pain-evoked behavior and attenuates stress response in rats subjected to craniotomy.

The 3-D configuration of excisional skin wound healing after topical probiotic application.

Nowadays, there is an increasing knowledge that probiotic bacteria, topically applied, affects skin pathology. The objective of this study is to evaluate the effect on wound healing of locally applied probiotics by calculating the 3-D configuration of a standardized excisional wound. Fifty-two male Wistar rats were randomly allocated into groups: control, PRO1 [L. plantarum] and PRO2 [L. rhamnosus, B. longum]. Six excisional full-thickness wounds were created on each dorsum by an 8-mm circular biopsy punch; probiotics or saline were applied on days 0, 2, 4, 8, 16, photos of the wounds taken and specimens excised for histology [4 rats/group/time-point]. Both probiotic-groups exhibited accelerated healing significantly faster than the control, throughout, PRO2 exhibiting finally the best results [day 16]. However, only on day 2, did PRO1 exhibit the best results [wounded area, borders distance and epitheliazation line]. The results clearly demonstrate that the topical application of probiotics significantly improves the healing process, each strain working differently and more effectively in different healing phases. Thus, a combined formula containing different probiotics to modulate various healing phases is desirable. To this end our research continous.

Osmotic nephrosis due to the use of anti-adhesive membrane intraperitoneally.

BACKGROUND: A common strategy for the prevention of intra-abdominal adhesions post-operatively has been the application of adhesion barriers into the peritoneal cavity. Side effects of these barriers are infection, abscesses and inadequate wound healing. There is no information about such a side effect of these materials on renal function. The aim of this study was to evaluate the effect of two different, commercially available polysaccharide-based anti-adhesive materials on renal function. METHODS: In 24 adult Wistar rats, an abdominal midline incision was performed, and an anti-adhesion membrane was placed in the peritoneal cavity so as to cover its whole surface. Four rats were used as the control group. In 12 rats, a membrane of macromolecular polysaccharides, weighing 40 mg/cm2, was placed intra-abdominally and in 8 rats, a hyaluronic acid-hydroacidmethylcellulose membrane weighing 0.4 mg/cm2 was placed. At 24 or 70 h, the rats were sacrificed, and we evaluated changes in serum creatinine, urea, uric acid, K and Na, and histologic examination of the kidney was performed. RESULTS: The use of the thicker macromolecular membrane was associated with a rise in serum creatinine and urea levels, vacuolization of all the tubular epithelial cells and mild interstitial infiltration. Rats in which the hyaluronic acid-hydroacidmethylcellulose membrane was used did not show any creatinine elevation, and they presented milder histologic lesions. CONCLUSION: Polysaccharide and cellulose anti-adhesive membrane cause renal damage with tubular cell vacuolization. The severity of kidney damage is relative to the quantity of the membrane material used.

Long-Term Effect of an Exercise Training Program on Physical Functioning and Quality of Life in Pulmonary Hypertension: A Randomized Controlled Trial.

The aim of this study was to evaluate the effects of a 6-month combined aerobic and strength exercise training program on functional and psychological aspects and health-related quality of life in patients with PH and to evaluate its longer-term impact. In total, 22 stable patients (mean age 53.9 ± 13.8, 13 female) with pulmonary hypertension of World Health Organization (WHO) class I-III participated in a nine-month study. They were randomly assigned into two groups: Group A participated in a 6-month combined aerobic and strength exercise training program, whereas Group B remained untrained. All patients underwent physical and psychological assessment at baseline and at month 6 (after completing the exercise program) and physical assessment after 9 months (3 months posttraining). After the 6-month exercise training program, patients of Group A significantly improved their physical (6MWD, STS 10 rep, STS 20 rep, TUG, lower limb strength, cardiopulmonary exercise time, METs, peak VO2, VCO2, and VE/VCO2 slope) and psychological aspects (SF-36, STAI, and BDI). Between the two groups, differences were observed at the 6MWD (95% CI: 36.2-64.6, η 2 = 0.72), STS 10 rep (95% CI: 6.6-2.2, η 2 = 0.4), STS 20 rep (95% CI: 10.8-2.4, η 2 = 0.34), lower limb strength (95% CI: 7.2-3.6, η 2 = 0.38), cardiopulmonary exercise time (95% CI: 0.1-3.3, η 2 = 0.2), and VCO2 (95% CI: 0.1-0.5, η 2 = 0.2). Additionally, psychological changes were noted at SF-36, PCS (95% CI: 3.6-14.8, η 2 = 0.35), MCS (95% CI: 1.3-16.1, η 2 = 0.22), TCS (95% CI: 1.3-16.1, η 2 = 0.22), and STAI (95% CI: 1.8-28.2, η 2 = 0.18). The favorable results of exercise were maintained at the 3-month posttraining follow-up assessment. No exercise-induced complications were observed throughout the study. In conclusion, a long-term exercise training program is a safe and effective intervention to improve functional status, psychological aspects, and health-related quality of life in patients with PH.

Implementation of Imaging Methods in Evaluation of T2DM-Correlated Brain Alterations and Cognitive Dysfunction.

INTRODUCTION: There has been mounting evidence that type 2 diabetes mellitus (T2DM) populations are prone to aberrant brain functionality and cognitive deficits. Hyperglycemic status and insulin resistance, among other factors, have been associated with compromised brain neural congruity, leading to lower cognitive performance. AIM: The aim of the present paper is to provide a comprehensive review of imaging techniques and their applicability in detection of brain changes in the setting of T2DM. METHODS: A search of PubMed electronic database was followed. Primary search terms included "imaging methods", "type 2 diabetes" and "cognitive impairment". RESULTS: A range of imaging modalities that can be of value in depiction of diabetes-mediated structural and functional brain aberrations. CONCLUSION: An increasingly body of research points to the adverse effect T2DM exerts on brain integrity and higher cognitive skills. Findings support the role of imaging techniques in delineation of brain divergence in middle-aged and older diabetic populations.

Toxic Environmental Factors and their Association with the Development of Dementia: a Mini Review on Heavy Metals and Ambient Particulate Matter.

INTRODUCTION: More and more studies are trying to establish a connection between dementia and environmental pollution. Dementia, most commonly associated with Alzheimer's disease, is a chronic, progressive, neurodegenerative disorder that is directly associated to aging. Although the etiology of the disease is not fully understood, it is recognized as a multifactorial one. Genetic and environmental factors contribute to the development of various forms of dementia. Both predisposing genes and environmental pollution have been shown to affect brain function through a variety of mechanisms. AIM: The purpose of this bibliographic work is «ecological consciousness¼ of modern societies to be awaken, to identify the harmful environmental factors and to highlight their involvement in the causal pathogenesis of the most debated disease, dementia. METHODS: Trying to achieve this aim, the available bibliography was reviewed and selected for further study. In particular, recent bibliographic data and scientific papers were selected, mainly from the last five years. The information was collected using the keywords "environmental pollution", " toxic agents" and "etiology of dementia", with particular emphasis on "Alzheimer's disease". The data were selected mainly from medical research databases. In particular, they were selected by PubMed, BioMed Central and Science Direct. CONCLUSION: According to the results of this study, long-term exposure of individuals to pollutants may be associated with an increased risk of dementia. However, we must be cautious in our conclusions, as further reliable studies are needed to confirm the stated evidence. Among other things, health professionals are responsible for promoting health, preventing and encouraging lifestyle change, so that the progressively growing elderly population remains autonomous, healthy and active.

Severity of Withdrawal Symptoms, Plasma Oxytocin Levels, and Treatment Outcome in Heroin Users Undergoing Acute Withdrawal.

Pre-clinical studies show that, following chronic opioid exposure, oxytocin neurons exhibit over-excitation upon withdrawal, causing an increase in oxytocin brain and plasma levels. Relevant clinical data on humans are scarce. This study investigates the opioid withdrawal stress effect on oxytocin plasma levels in humans. We evaluated 57 male chronic heroin users in a residential detoxification program. We determined plasma oxytocin levels by ELISA and measured the stress effects of withdrawal using the COWS scale for opioid withdrawal, the VAS scale for craving, and the Hamilton scales for anxiety and depression on the second day of admission. Out of the 57 patients enrolled in the study, 27 completed the 21-day program, while the remaining 30 dropped out prior to completion. Plasma oxytocin levels were significantly higher in those individuals who dropped out than in those who completed the program. Participants who dropped out at some stage scored higher in the COWS, VAS-Craving, and Hamilton-anxiety scales, indicating a higher stress and explaining the higher oxytocin levels. In addition, plasma oxytocin levels correlated positively with the scores achieved in the COWS and Hamilton-anxiety scales. Higher withdrawal stress levels are associated with higher plasma oxytocin levels and early treatment discharge.

Serum estradiol, progesterone, testosterone, FSH and LH levels in postmenopausal women with Alzheimer's dementia.

Several studies have suggested that estrogen replacement therapy lowers the risk of Alzheimer's dementia (AD) among postmenopausal women. Other studies have evaluated serum levels of sex hormones and gonadotropins in women with AD. Estrogens (E(1) and E(2)), luteinizing hormone (LH) and follicular stimulating hormone (FSH), dihydroepiandrosterone and sex hormone binding albumin, which normally responds to circulating testosterone, have been investigated by others using the same protocol in postmenopausal women with AD, older than 65 years. Others have studied in elderly women with AD, also using one protocol, fewer sex hormones and/or gonadotropins. We have studied the serum levels of estradiol, progesterone, testosterone, LH and FSH in the same serum sample of postmenopausal women with AD and other dementias and compared them to a group of controls. We are not aware of a similar study in the literature. All patients were diagnosed on clinical grounds and screened by the mini mental score examination (MMSE). Forty eight women had AD (Group A), mean age 72 years and age range 60-84 years, s even had other types of dementia (Group B), mean age 63.5 years and age range 53-74 years and 33 women had no cognitive impairment and were studied as controls (Group C). Group C women had mean age of 65 years and their age ranged between 55-73 years. Estradiol, progesterone and testosterone were measured by radioimmunoassay (RIA), while FSH and LH by radioimmunometric assay (IRMA). Our results showed that estradiol was significantly lower in Group A as compared to Group C (P=0.04). There was no significant difference in the levels of the other four hormones in the three Groups as studied by the Mann-Whitney U and the Pearson's statistical test. Our results were not influenced by differences due to sex, age, ethnic group or education since these factors were either similar or comparable in all Groups studied. All but two of the subjects, with mild alcoholism, smoking, increased BMI and chronic diseases, had all five hormones studied within reference limits. We consider that the absence of difference we found in the four hormone levels, in Groups A, B and C may be related to free hormones, to the different stage of AD of our patients, to intra assay variability, to assay sensitivity or to other non specified factors. Future study may be directed towards whether a primary or secondary hypogonadism exists in AD and whether hormones are contributing to or are the result of brain degeneration in AD.

Efficiency of different decalcification protocols for nasal osseous structures in a rat experimental model of allergic rhinitis, and their effects on epithelial histology: an attempt at standardization.

INTRODUCTION: Decalcification of osseous specimens is required for histological analysis; this however may cause tissue damage. In rodent models of allergic rhinitis (AR), epithelial histologic assessment necessitates prior decalcification of the nasal osseous structures. However, respiratory epithelium is highly susceptible to damage, and rat nasal architecture is elaborate and its sectioning is challenging. Nevertheless, decalcification is not standardized in experimental AR. We therefore undertook this task, in order to reduce experimental bias. METHODS: Six-to-eight week-old Wistar rats underwent an AR protocol. Subsequently, nasal structures were decalcified in the following mediums: (i) formic acid 10% for 5 and 20 days; (ii) formic acid 15% for 5 and 15 days; (iii) Morse Solution for 5 and 20 days and (iv) EDTA for 20 and 40 days. Decalcification efficiency/speed was evaluated via radiographic analysis. Furthermore, specimens were stained with hematoxylin and eosin and assessed for preservation of epithelial features. RESULTS: Specimens were appropriately decalcified in 5 days in the formic acid-based mediums and in 20 days in EDTA with minimal epithelial damage. EDTA for 40 days had no unacceptable adverse effects; conversely, 15 and/or 20 days in acid-based agents provided no extra benefit for decalcification and were detrimental to the epithelium. CONCLUSIONS: EDTA treatment for 20 days is appropriate for decalcification of nasal structures in rat models of allergic rhinitis; further incubation preserves epithelial integrity but is not required. When urgency is a factor, formic-acid-based decalcification for 5 days yields acceptable results.