Improved femoral micro-architecture in adult male individuals with overweight: fracture resistance due to regional specificities.

BACKGROUND: It is still unclear whether femoral fracture risk is positively or negatively altered in individuals with overweight. Considering the lack of studies including men with overweight, this study aimed to analyze regional specificities in mechano-structural femoral properties (femoral neck and intertrochanteric region) in adult male cadavers with overweight compared to their normal-weight age-matched counterparts. METHODS: Ex-vivo osteodensitometry, micro-computed tomography, and Vickers micro-indentation testing were performed on femoral samples taken from 30 adult male cadavers, divided into the group with overweight (BMI between 25 and 30 kg/m2; n = 14; age:55 ± 16 years) and control group (BMI between 18.5 and 25 kg/m2; n = 16; age:51 ± 18 years). RESULTS: Better quality of trabecular and cortical microstructure in the inferomedial (higher trabecular bone volume fraction, trabecular thickness, and cortical thickness, coupled with reduced cortical pore diameter, p < 0.05) and superolateral femoral neck (higher trabecular number and tendency to lower cortical porosity, p = 0.043, p = 0.053, respectively) was noted in men with overweight compared to controls. Additionally, the intertrochanteric region of men with overweight had more numerous and denser trabeculae, coupled with a thicker and less porous cortex (p < 0.05). Still, substantial overweight-induced change in femoral osteodensitometry parameters and Vickers micro-hardness was not demonstrated in assessed femoral subregions (p > 0.05). CONCLUSIONS: Despite the absence of significant changes in femoral osteodensitometry, individuals with overweight had better trabecular and cortical femoral micro-architecture implying higher femoral fracture resistance. However, the microhardness was not significantly favorable in the individuals who were overweight, indicating the necessity for further research.

Penile Pearls and Pearling: Characteristics and Social Identity from the Perspective of Forensic Pathologists.

Penile pearls are artificial implants placed beneath the skin of a penis to provide enhanced sexual experience for the partner or present a stigma of a particular social subgroup (e.g., prisoner, member of a gang). This genital modification is usually encountered in men of low socioeconomic status and prisoners who might (self) implant improvised pearls under poor sanitary conditions. We have only recently started to encounter penile pearls on autopsy, incidentally. The aim of this study was to analyze our autopsy cases with penile pearls to assess the characteristics of these subjects regarding their socioeconomic status, history of imprisonment, substance abuse, as well as the characteristics of implants. Nineteen men were included. Most were born in the 1970s and 1980s, with only elementary/vocational school education (n = 10). Only five men graduated from high school. At least 14 were in prison at some point in life and 13 were unemployed. Ten men were unmarried. In 11 men, regular alcohol consumption was reported. 12 used illicit substances, most with a history of heroin injection. Penile pearls were improvised and made of rigid plastic in 10 men, eight were of soft silicone-like material, and one was of metal. A distinct characteristic was a ribbed contour of some implants. Although this genital modification seems to gain more attention outside of described vulnerable groups, it mostly remains limited to them in our region. It is most likely performed in improvised, non-professional, unsanitary conditions, probably in prisons.

The impact of different diuretics on regression of myocardial reperfusion injury in spontaneously hypertensive rats.

The study's objective was to ascertain the results of sub-chronic therapy of various diuretics on the ischemia/reperfusion dysfunction of the heart in hypertensive rats by a global ischemia in an isolated rat heart model. The research included 40 spontaneously hypertensive male rats (Wistar Kyoto strain, body mass 250 ± 30 g, 8 weeks old) grouped into four groups. The animals were treated for 4 weeks with 10 mg/kg of hydrochlorothiazide, indapamide, or spironolactone per os. After a period of sub-chronic treatment, we analyzed hemodynamic measurements, echocardiography, and myocardial function according to the Langendorff retrograde perfusion method. The hearts were subjected to 20 min of global ischemia and then reperfused for 30 min (I20:R30). Cardiovascular parameters that depict the left ventricle functions were continuously monitored, while flowmetry was used to determine coronary flow values. Markers of oxidative stress were estimated from coronary venous effluent using spectrophotometry. All three examined diuretics (hydrochlorothiazide, spironolactone, indapamide) lowered the production of the majority of the detected prooxidants, reducing myocardial oxidative damage. The cardiological examination of heart function in vivo demonstrated that treatment with indapamide and spironolactone mitigates left ventricular hypertrophy but without significant lowering of blood pressure or increment in ejection fraction. Additionally, monitoring of cardiac function ex vivo indicated the cardiodepressant effect of spironolactone in spontaneously hypertensive rats.

Effects of direct pulp capping with recombinant human erythropoietin and/or mineral trioxide aggregate on inflamed rat dental pulp.

OBJECTIVE: This study aimed to evaluate the dental pulp responses to recombinant human erythropoietin (rhEPO) and/or mineral trioxide aggregate (MTA) in pulp capping of inflamed dental pulp in vivo. MATERIALS AND METHODS: In accordance with ARRIVE guidelines, pulp inflammation was induced by exposing the maxillary first molars (n = 64) of Wistar rats (n = 32) to the oral environment for two days. The exposed pulps were randomly assigned four groups based on the pulp capping material: rhEPO, MTA, MTA + rhEPO, or an inert membrane. An additional eight rats formed the healthy control group. After four weeks, the animals were euthanized, and histological, qRT-PCR, and spectrophotometric techniques were employed to analyze the left maxillary segments, right first maxillary molars, and blood samples, respectively. Statistical significance was set at p < 0.05 and < 0.001. RESULTS: Pulp capping with rhEPO, MTA, or MTA + rhEPO resulted in lower inflammation and higher mineralization scores compared to untreated control. MTA + rhEPO group exhibited significantly decreased expression of tumor necrosis factor-alpha, and interleukin 1-beta, while MTA group showed substantially reduced expression of interferon-gamma. Both rhEPO and MTA + rhEPO groups presented elevated dentin matrix protein 1 levels compared to untreated control. Furthermore, pulp capping with rhEPO and/or MTA led to increased transforming growth factor-beta 1 expression and reductions of pro-inflammatory/immunoregulatory cytokine ratios and prooxidative markers. Pulp capping with rhEPO also resulted in increase of systemic antioxidative stress markers. CONCLUSION: Capping with rhEPO or MTA + rhEPO resulted in a favorable effect that was similar or even superior to that of MTA.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

Extensive direct spreading of "groin hit"-related soft tissue infections: a report of three cases.

We present fatal extensive soft tissue infections, a consequence of groin heroin injection, in three subjects, who were 27, 34, and 39 years old and had a history of over 10-, 15-, and 5-years of heroin injection (cases 1, 2, and 3, respectively). In all cases, the first symptoms of the infection appeared at least a week prior, with rapid deterioration on the last day. The hallmark was a disproportion between external and internal findings in the affected thighs. The latter presented as extensively spread suppurative inflammation with soft tissue necrosis. In case 1, subtle skin erythema was present in the left groin, with a wound suggestive of a recent abscess incision and injection-related scarring. However, dissection revealed that inguinal regions and deep soft tissue (including the muscle sheets) of the left thigh, gluteal region, and lower third of the anterior abdominal wall were inflamed with pus, alongside fibrinopurulent peritonitis. Case 2 had pronounced erythema and swelling of the thigh and knee. Diffuse suppuration was observed upon dissection in the inguinal regions, which extended into the iliopsoas muscles, with soft tissue and muscle necrosis. In the abdominal cavity, we detected 150 mL of serofibrinous exudate. Only case 3 had a prominent, 4 × 3.5-cm necrotic skin defect through which pus spontaneously drained. In contrast to the other two, although extensive pus collection within predominantly necrotic thigh's soft tissue was present, the inflammation did not expand above the inguinal ligament, and peritonitis was not observed. Toxicology analysis excluded acute heroin intoxications.

Changes in Left Ventricular Ejection Fraction and Oxidative Stress after Phosphodiesterase Type-5 Inhibitor Treatment in an Experimental Model of Retrograde Rat Perfusion.

Background and objectives: Taking into consideration the confirmed role of oxidative stress in ischemia/reperfusion injury and the insufficiency in knowledge regarding the phosphodiesterase 5 (PDE5)-mediated effects on the cardiovascular system, the aim of our study was to investigate the influence of two PDE5 inhibitors, tadalafil and vardenafil, with or without the addition of N(G)-nitro-L-arginine methyl ester (L-NAME), on oxidative stress markers, coronary flow and left ventricular function, both ex vivo and in vivo. Methods: This study included 74 male Wistar albino rats divided into two groups. In the first, 24 male Wistar rats were orally treated with tadalafil or vardenafil for four weeks in order to perform in vivo experiments. In the second, the hearts of 50 male Wistar albino were excised and perfused according to the Langendorff technique in order to perform ex vivo experiments. The hearts were perfused with tadalafil (10, 20, 50 and 200 nM), vardenafil (10, 20, 50 and 200 nM) and a combination of tadalafil/vardenafil and L-NAME (30 µM). The CF and oxidative stress markers, including nitrite bioaviability (NO2-), superoxide anion radical (O2-), and the index of lipid peroxidation, were measured in coronary effluent. Results: The L-arginin/NO system acts as the mediator in the tadalafil-induced effects on the cardiovascular system, while it seems that the vardenafil-induced increase in CF was not primarily induced by the NO system. Although tadalafil induced an increase in O2- in the two lowest doses, the general effects of both of the applied PDE5 inhibitors on oxidative stress were not significant. The ejection function was above 50% in both groups. Conclusions: Our results showed that both tadalafil and vardenafil improved the coronary perfusion of the myocardium and LV function by increasing the EF.

The Enhanced Effects of Swimming and Running Preconditioning in an Experimental Model of Myocardial Ischemia/Reperfusion Injury.

Background and Objectives: This study was conducted to examine the influence of different swimming and running protocols as forms of physiological preconditioning on an isolated rat heart's ischemia/reperfusion injury. Materials and Methods: This study was conducted on 60 male Wistar albino rats (6 weeks old, bw: 200 ± 20 g), divided into: CTRL group-a sedentary control group; sAeT-a group that underwent aerobic swimming conditioning using a swimming protocol for 8 weeks; sAnT-a group that underwent anaerobic swimming conditioning; rAeT-a group that underwent aerobic running conditioning; and rAnT-a group that underwent anaerobic running conditioning. After the preconditioning protocols, ex vivo estimating of myocardial function according to the Langendorff technique was performed. Results: The anaerobic running training decreased heart rate and the anaerobic swimming training reduced coronary flow, demonstrating the difference in the physiological heart response of aerobic/anaerobic physical training (p < 0.05). Heart rate was significantly reduced in both training swimming groups after a period of ischemia (p < 0.05). On the other hand, the anaerobic running protocol induced a significantly decreased heart rate in comparison with the aerobic running group and the sedentary group (p < 0.05). Conclusions: The data from this experimental study support many protective training effects, i.e., improved contractility, improved resting heart rate, and increased physical work capacity and exercise tolerance. Physical training in the form of anaerobic running induces greater heart preconditioning for reperfusion injury in comparison with anaerobic swimming training.

High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats.

Background and Objectives: Polycystic ovary syndrome (PCOS) is a frequent multifactorial endocrinopathy affecting women in the reproductive period, often associated with infertility and metabolic disorders. The use of animal models helps to better understand etiopathogenesis, enabling the examination of the effects of certain drugs in order to discover the best possible therapeutic approach. We tried to investigate the additional effect of estradiol-valerate (EV) and high-fat diet (HFD) in female rats to explore PCOS-related alterations with special focus on oxidative stress. Materials and Methods: Animals were divided into three groups: control group (CTRL, n = 6), estradiol-valerate group (EV, n = 6), and estradiol-valerate group on HFD (EV + HFD, n = 6). PCOS was induced by single subcutaneous injection of long-acting EV in a dose of 4 mg/per rat. We tried to improve the metabolic characteristics of the PCOS animal model by adding HFD, so the CTRL and EV group had a regular diet, while the EV + HFD group had HFD during the induction period of 60 days. Results: We observed alterations of anthropometric parameters and hormonal disturbances, along with estrus cycle impairment reassembly to obese-type PCOS phenotype. Moreover, glucose metabolism was impaired after addition of HFD to EV protocol, contrary to EV administered alone. Histological analysis confirmed more numerous cystic follicles after the combination of EV and HFD protocol. The alterations of oxidative stress markers could be related to and serve as the mechanistic base for development of PCOS-related endocrine, reproductive, and metabolic properties. Conclusions: The additive effect of EV and HFD was obvious in the majority of the parameters observed. Our study strongly demonstrated metabolic as well as reproductive properties of PCOS in rats.

Micro-scale assessment of bone quality changes in adult cadaveric men with congestive hepatopathy.

Congestive hepatopathy (CH) is a chronic liver disease (CLD) caused by impaired hepatic venous blood outflow, most frequently resulting from congestive heart failure. Although it is known that heart failure and CLDs contribute to increased risk for age-related fractures, an assessment of CH-induced skeletal alterations has not been made to date. The aim of our study was to characterize changes in bone quality in adult male cadavers with pathohistologically confirmed CH compared with controls without liver disease. The anterior mid-transverse part of the fifth lumbar vertebral body was collected from 33 adult male cadavers (age range 43-89 years), divided into the CH group (n = 15) and the control group (n = 18). We evaluated trabecular and cortical micro-architecture and bone mineral content (using micro-computed tomography), bone mechanical competence (using Vickers micro-hardness tester), vertebral cellular indices (osteocyte lacunar network and bone marrow adiposity), and osteocytic sclerostin and connexin 43 expression levels (using immunohistochemistry staining and analysis). Deterioration in trabecular micro-architecture, reduced trabecular and cortical mineral content, and decreased Vickers microhardness were noted in the CH group (p < 0.05). Reduced total number of osteocytes and declined connexin 43 expression levels (p < 0.05) implied that harmed mechanotransduction throughout the osteocyte network might be present in CH. Moreover, elevated expression levels of sclerostin by osteocytes could indicate the role of sclerostin in mediating low bone formation in individuals with CH. Taken together, these micro-scale bone alterations suggest that vertebral strength could be compromised in men with CH, implying that vertebral fracture risk assessment and subsequent therapy may need to be considered in these patients. However, further research is required to confirm the clinical relevance of our findings.

The altered osteocytic expression of connexin 43 and sclerostin in human cadaveric donors with alcoholic liver cirrhosis: Potential treatment targets.

Previous studies suggested that osteocyte lacunar network disruption could play a role in the complex pathophysiology of bone changes in aging and disease. Considering that particular research interest is lacking, we aimed to assess alcoholic liver cirrhosis (ALC)-induced changes in osteocyte lacunar network and bone marrow adiposity. Immunohistochemistry was conducted to assess changes in the micro-morphology of osteocyte lacunar network and bone marrow adiposity, and expression of connexin 43 and sclerostin in vertebral and femoral samples collected from 40 cadaveric men (age range between 44 and 70 years) divided into ALC group (n = 20) and control group (n = 20). Furthermore, the assessment of the potential association between bone changes and the severity of the hepatic disorder (given by Knodell's pathohistologic scoring) was conducted. Our data revealed fewer connexin 43-positive osteocytes per vertebral and femoral bone area (p < 0.01), suggesting defective signal transduction among osteocytes in ALC individuals. Moreover, we found an ALC-induced increase in the number of adipocytes in the vertebral bone marrow (p = 0.038). Considering significant associations between the severity of liver tissue disturbances and impaired functionality of osteocyte lacunar network (Pearson's correlation analyses, p < 0.05), we may assume that timely treatment of the liver disease may delay bone impairment. ALC induced an increase in osteocytic sclerostin expression (p < 0.001), suggesting its role in mediating low bone formation among ALC individuals. Hence, medicaments targeting low bone formation may be beneficial to attenuate the bone changes among ALC patients. However, future clinical studies are required to verify the therapeutic utility of these findings.

SGLT2 inhibitors: a focus on cardiac benefits and potential mechanisms.

This paper highlights the cardioprotective potential of sodium-glucose cotransporter 2 inhibitors (SLGT2i), as well as several most discussed mechanisms responsible for their cardioprotection. Cardiovascular diseases are considered a primary cause of death in nearly 80% of type 2 diabetes mellitus (T2DM) patients, with a 2-4-fold greater incidence of heart failure (HF) among diabetics. As novel hypoglycemics, SGLT2i showed exceptional cardiovascular benefits, reflected through robust reductions of cardiovascular mortality and hospitalization for HF in T2DM patients. Recently, those effects have been reported even in patients with HF and reduced ejection fraction irrespectively of diabetic status, suggesting that cardioprotective effects of SGLT2i are driven independently of their hypoglycemic actions. SGLT2i exerted hemodynamic and metabolic effects, partially driven by natriuresis and osmotic diuresis. However, those systemic effects are modest, and therefore cannot be completely related to the cardiac benefits of these agents in T2DM patients. Hence, increased circulating ketone levels during SGLT2i administration have brought out another hypothesis of a cardiac metabolic switch. Moreover, SGLT2i influence ion homeostasis and exert anti-inflammatory and antifibrotic effects. Their enviable influence on oxidative stress markers, as well as anti- and pro-apoptotic factors, have also been reported. However, since the main mechanistical contributor of their cardioprotection has not been elucidated yet, a joint action of systemic and molecular mechanisms has been suggested. In the light of ongoing trials evaluating the effects of SGLT2i in patients with HF and preserved ejection fraction, a new chapter of beneficial SGLT2i mechanisms is expected, which might resolve their main underlying action.

Increased Cortical Porosity, Reduced Cortical Thickness, and Reduced Trabecular and Cortical Microhardness of the Superolateral Femoral Neck Confer the Increased Hip Fracture Risk in Individuals with Type 2 Diabetes.

Individuals with diabetes mellitus type 2 (T2DM) have approximately 30% increased risk of hip fracture; however, the main cause of the elevated fracture risk in those subjects remains unclear. Moreover, micromechanical and microarchitectural properties of the superolateral femoral neck-the common fracture-initiating site-are still unknown. We collected proximal femora of 16 men (eight with T2DM and eight controls; age: 61 ± 10 years) at autopsy. After performing post-mortem bone densitometry (DXA), the superolateral neck was excised and scanned with microcomputed tomography (microCT). We also conducted Vickers microindentation testing. T2DM and control subjects did not differ in age (p = 0.605), body mass index (p = 0.114), and femoral neck bone mineral density (BMD) (p = 0.841). Cortical porosity (Ct.Po) was higher and cortical thickness (Ct.Th) was lower in T2DM (p = 0.044, p = 0.007, respectively). Of trabecular microarchitectural parameters, only structure model index (p = 0.022) was significantly different between T2DM subjects and controls. Control group showed higher cortical (p = 0.002) and trabecular bone microhardness (p = 0.005). Increased Ct.Po and decreased Ct.Th in T2DM subjects increase the propensity to femoral neck fracture. Apart from the deteriorated cortical microarchitecture, decreased cortical and trabecular microhardness suggests altered bone composition of the superolateral femoral neck cortex and trabeculae in T2DM. Significantly deteriorated cortical microarchitecture of the superolateral femoral neck is not recognized by standard DXA measurement of the femoral neck.

Vascular Complications in Individuals with Type 2 Diabetes Mellitus Additionally Increase the Risk of Femoral Neck Fractures Due to Deteriorated Trabecular Microarchitecture.

Individuals with diabetes mellitus type 2 (T2DM) have an increased risk of hip fracture, especially if vascular complications are present. However, microstructural origins of increased bone fragility in T2DM are still controversial. DXA measurement of the contralateral hip and three-dimensional microCT analyses of femoral neck trabecular microarchitecture were performed in 32 individuals (26 women and 6 men, 78 ± 7 years). The specimens were divided to two groups: T2DM individuals with hip fracture (DMFx, n = 18) and healthy controls (CTL, n = 14). DMFx group consisted of individuals with vascular complications (DMFx_VD, n = 8) and those without vascular complications (DMFx_NVD, n = 10). T-score was significantly lower in DMFx_VD and DMFx_NVD than in controls (p < 0.001). BV/TV, Tb.N, Tb.Sp, SMI, and FD varied among DMFx_NVD, DMFx_VD, and CTL groups (p = 0.023, p = 0.004, p = 0.008, p = 0.001, p = 0.007, respectively). Specifically, BV/TV of DMFx_VD was significantly lower than that of DMFx_NVD group (p = 0.020); DMFx_NVD group had higher Tb.N and lower Tb.Sp compared with DMFx_VD (p = 0.006, p = 0.012, respectively) and CTL (p = 0.026, p = 0.035, respectively). DMFx group and healthy controls showed similar BV/TV, Tb.Th, Tb.N, Tb.Sp, Conn.D, DA, and FD (p = 0.771, p = 0.503, p = 0.285, p = 0.266, p = 0.208, p = 0.235, p = 0.688, respectively), while SMI was significantly higher in controls (p = 0.005). Two distinct phenotypes of bone fragility were identified in T2DM patients: patients with vascular complications showed impaired trabecular microarchitecture, whereas bone fragility in the group without vascular complications was independent on trabecular microarchitecture pattern. Such heterogeneity among T2DM patients may explain contradicting literature data and may set a basis for further studies to evaluate fracture risk related to T2DM.

Creatine phosphate administration in cardiac ischemia-reperfusion injury in rats: focus on differences between preconditioning, perconditioning, and postconditioning protocols.

The aim of this study was to examine and compare the influence of preconditioning, perconditioning, and postconditioning with creatine phosphate (PCr) on functional recovery and production of prooxidants in isolated rat hearts subjected to ex vivo ischemic-reperfusion (I-R) injury on a Langendorff apparatus. Wistar albino rats (male, n = 40) were divided into four groups: control and groups in which PCr (0.5 mmol/L, 5 min) was perfused before (Pre group), after (Post group), or during (Per group) ex vivo induced ischemia. PCr application was associated with the great benefits of preserving cardiac contractility (in Pre group 100.96% for +(dP/dt max) and 97.61% for -(dP/dt max), in Per group 96.72% for +(dP/dt max) and 95.60% for -(dP/dt max), and in Post group 143.84% for +(dP/dt max) and 104.36% for -(dP/dt max) in relation to the stabilization). In addition, PCr application prevented the increase in prooxidative markers during I-R injury in all therapeutic modalities. The most intensive benefits in the current investigation were observed when PCr was applied during the period of ischemia because the lowest fluctuations in the parameters of cardiac function and oxidative stress were observed. Overall, the results of this study highlight PCr-induced cardioprotection with promising prospects for future clinical use.

Potential role of d-chiro-inositol in reducing oxidative stress in the blood of nonobese women with polycystic ovary syndrome.

d-chiro-Inositol (DCI), an isomer of inositol, possesses antioxidative and endothelial protective properties. Possibly due to a deficiency of insulin mediators, polycystic ovary syndrome (PCOS) is often associated with insulin resistance (IR) and hyperinsulinemia, likely responsible for an elevated production of reactive oxygen species. We investigated oxidative-related alterations of inositol in the blood of women with PCOS before and after treatment with DCI. A total of 38 normal-weight PCOS women were investigated before and after DCI administration (500 mg/day for 12 weeks; n = 38) by evaluating serum testosterone, serum androstenedione, fasting serum insulin, fasting serum glucose, and parameters of IR. From the blood, we determined biomarkers of oxidative stress: superoxide anion radicals, hydrogen peroxide, nitric oxide, and the index of lipid peroxidation. The activity of catalase and superoxide dismutase and the reduced glutathione (GSH) content in the hemolysate were also assessed. Data showed that PCOS patients' plasma underwent oxidative stress, as indicated by the higher level of prooxidants and reduced cytosolic GSH content. DCI treatment significantly improved the metabolic parameters. Also, serum values of testosterone were reduced. In conclusion, PCOS patients suffer from a systemic oxidative stress that induces endothelial dysfunction. Treatment with DCI is effective in reducing hormonal, metabolic, and oxidative abnormalities in PCOS patients by improving IR.

Guanidinoacetic acid provides superior cardioprotection to its combined use with betaine and (or) creatine in HIIT-trained rats.

This study aimed to determine how guanidinoacetic acid (GAA) or its combined administration with betaine (B) or creatine (C) influences the cardiac function, morphometric parameters, and redox status of rats subjected to high-intensity interval training (HIIT). This research was conducted on male Wistar albino rats exposed to HIIT for 4 weeks. The animals were randomly divided into five groups: HIIT, HIIT + GAA, HIIT + GAA + C, HIIT + GAA + B, and HIIT + GAA + C + B. After completing the training protocol, GAA (300 mg/kg), C (280 mg/kg), and B (300 mg/kg) were applied daily per os for 4 weeks. GAA supplementation in combination with HIIT significantly decreased the level of both systemic and cardiac prooxidants ( O 2 - , H2O2, NO 2 - , and thiobarbituric acid reactive substances) compared with nontreated HIIT (p < 0.05). Also, GAA treatment led to an increase in glutathione and superoxide dismutase levels. None of the treatment regimens altered cardiac function. A larger degree of cardiomyocyte hypertrophy was observed in the HIIT + GAA group, which was reflected through an increase of the cross-sectional area of 27% (p < 0.05) and that of the left ventricle wall thickness of 27% (p < 0.05). Since we showed that GAA in combination with HIIT may ameliorate oxidative stress and does not alter cardiac function, the present study is a basis for future research exploring the mechanisms of cardioprotection induced by this supplement in an HIIT scenario.

Effects of Combined Allogenic Adipose Stem Cells and Hyperbaric Oxygenation Treatment on Pathogenesis of Osteoarthritis in Knee Joint Induced by Monoiodoacetate.

The beneficial effects of HBO in inflammatory processes make it an attractive type of treatment for chronic arthritis. In addition, the effects of combination therapy based on adipose stem cells and HBO on OA progression have not been fully investigated. The current study explored the efficacy of intra-articular injection of allogeneic adipose-derived mesenchymal stem cells (ADMSCs) combined with hyperbaric oxygenation treatment (HBO) in a rat osteoarthritis (OA) model. The rat OA model was induced by intra-articular injection of monoiodoacetate (MIA) and 7 days after application of MIA rats were divided into five groups: healthy control (CTRL), osteoarthritis (OA), ADMSCs (ADS), the HBO+ADS21day and HBO+ADS28day groups. A single dose of 1 × 106 allogeneic ADMSCs suspended in sterile saline was injected into the knee joint alone or in combination with HBO treatment. Rats were sacrificed at 3 or 4 weeks after MIA injection. Treatment outcomes were evaluated by radiographic, morphological and histological analysis and by specific staining of articular cartilage. We also measured the level of inflammatory and pro/antioxidative markers. We confirmed that combined treatment of ADMSCs and HBO significantly improved the regeneration of cartilage in the knee joint. Rtg score of knee joint damage was significantly decreased in the HBO+ADS21day and HBO+ADS28day groups compared to the OA. However, the positive effect in the HBO+ADS28day group was greater than the HBO+ADS21day group. The articular cartilage was relatively normal in the HBO+ADS28day group, but moderate degeneration was observed in the HBO+ADS21day compared to the OA group. These findings are in line with the histopathological results. A significantly lower level of O2-. was observed in the HBO+ADS28day group but a higher NO level compared to the HBO+ADS21day group. Moreover, in the HBO+ADS28day group significantly higher concentrations of IL-10 were observed but there was no significant difference in proinflammatory cytokine in serum samples. These results indicate that a single intra-articular injection of allogeneic ADMSCs combined with HBO efficiently attenuated OA progression after 28 days with greater therapeutic effect compared to alone ADMSCs or after 3 weeks of combined treatment. Combined treatment might be an effective treatment for OA in humans.

The Evaluation of Healing Properties of Galium verum-Based Oral Gel in Aphthous Stomatitis in Rats.

Although oral ulcers represent one of the most frequent oral mucosal diseases, the available treatment is not sufficient to provide complete ulcer recovery without side-effects. Therefore, the aim of our study was to prepare a mucoadhesive oral gel based on Galium verum ethanol extract (GVL gel) and reveal its healing effects in the model of aphthous stomatitis in rats. Rats with oral ulcers were divided into the following groups: control (untreated), gel base (ulcer was treated with the gel base, three times per day for 10 days), and GVL gel group (the ulcer was treated with GVL gel in the same way as the gel base). Animals from each group were sacrificed on days 0, 3, 6, and 10 for collecting blood and ulcer tissue samples. Healing properties of oral gel were determined by clinical evaluation, as well as biochemical and histopathological examinations. Our findings suggest a significant decrease in the ulcer size in GVL gel group, with healing effects achieved through the alleviation of oxidative stress, reduction in COX-2 immunopositivity, and increase in collagen content in buccal tissue. Significant ulcer repairing potential of GVL gel highlights this oral mucoadhesive gel as a promising tool for prevention and treatment of RAS.

Subendocardial hemorrhages in a case of complete avulsion of the heart.

We present a case of a 66-year-old man who died on the scene in a traffic accident. He was a car driver involved in a head-on collision with a bus. Autopsy performed 4 days after death showed multiple head, torso, and limb injuries, including complete avulsion of the heart from the great vessels and avulsion of both lungs from the tracheobronchial tree due to rapid deceleration. Gross examination of the heart was remarkable for patchy hemorrhages beneath the endocardium involving the left side of the interventricular septum and papillary muscles. Histological examination identified streaky subendocardial hemorrhages and perivascular hemorrhages in the subendocardial myocardium. Since the death, in this case, was instantaneous, the most likely mechanism of subendocardial hemorrhages involved a precipitous decrease in left ventricle pressure, as it is improbable that the timeline of events allowed for a catecholamine surge to occur and take effect. Findings in this case also suggest that subendocardial hemorrhages are an indicator of intravital trauma and that the time required for them to develop is very short.