Looking at the Golden Ratio from the Blood Pressure Perspective: Assessing the Hypertensive Patients and Normotensive Subjects.

BACKGROUND: The representatives of mathematical concepts and indices allied to the Golden Ratio (GR) have been shown in the human body in superimposed human hands, phalangeal lengths of the digits, human ears, and the cardiovascular system. Recently, it has been demonstrated that the systolic blood pressure (SBP) to diastolic blood pressure (DBP) ratio measured by ambulatory blood pressure monitoring (ABPM) is close to GR. Accordingly, we aimed to evaluate the ratios between the SBP, DBP, and PP in normotensive and hypertensive patients who were on medical treatment or not, to assess the existence of golden proportions in 24-hour ambulatory blood pressure monitoring results. MATERIAL AND METHOD: Five hundred and twenty-nine patients who underwent ABPM were retrospectively enrolled in the study population. The ABPM was programmed to measure blood pressure every 30 min during the daytime and 60 min night time. Based on the ABPM results, patients were classified as hypertensive (SBP/DBP≥130/80 mmHg) and normotensive (SBP/DBP<130/80 mmHg), depending on ESC/ESH 2018 guidelines. They were also divided into two subgroups: medicated and nonmedicated. Systolic to diastolic blood pressure ratio (SBP/DBP) and diastolic blood pressure to pulse pressure (DBP/PP) were calculated in the usual fashion in all study populations and subgroups. RESULTS: After the exclusion of 133 patients who did not fulfill the inclusion criteria, 396 patients were included in the statistical analysis. Mean SBP/DBP ratios were 1.66±0.15 in all the study population, 1.63±0.11 in normotensive without medication, 1.66±0.13 in normotensive with medications, 1.62±0.15 in hypertensive without medication, and 1.76±0.20 with medications. CONCLUSION: We have documented that SBP to DBP ratios of untreated patients, irrespective of having normal or high blood pressure, run close around the GR. However, SBP to DBP ratios of patients having antihypertensive treatment are far from the GR.

Ignored Role of Paroxysmal Atrial Fibrillation in the Pathophysiology of Cryptogenic Stroke in Patients with Patent Foramen Ovale and Atrial Septal Aneurysm.

The association between cryptogenic stroke (CS) and patent foramen ovale (PFO) with or without atrial septal aneurysm (ASA) has been a debate for decades in terms of pathophysiologic processes and clinical courses. This issue has become more interesting and complex, because of the concerns associating the CS with so-called normal variant pathologies of interatrial septum, namely ASA and PFO. While there is an anatomical pathology in the interatrial septum, namely PFO and ASA, the embolic source of stroke is not clearly defined. Moreover, in patients with PFO and CS, the risk of recurrent stroke has also been associated with other PFOunrelated factors, such as hyperlipidemia, body mass index, diabetes mellitus, and hypertension, leading to the difficulty in understanding the pathophysiologic mechanism of CS in patients with PFO and/or ASA. Theoretically, the embolic source of cryptogenic stroke in which PFO and/or ASA has been involved can be categorized into three different anatomical locations, namely PFO tissue and/or ASA tissue itself, right or left atrial chambers, and venous vascular territory distal to the right atrium, i.e., inferior vena cava and lower extremity venous system. However, the possible role of paroxysmal atrial fibrillation associated with PFO and/or ASA as a source of cryptogenic stroke has never been mentioned clearly in the literature. This review aims to explain the association of cryptogenic stroke with PFO and/or ASA in a comprehensive manner, including anatomical, clinical, and mechanistic aspects. The potential role of paroxysmal atrial fibrillation and its contribution to clinical course have been also discussed in a hypothetical manner to elucidate the pathophysiology of CS and support further treatment modalities.

Experimental infection of Mongolian gerbils with Toxoplasma gondii: pathological and immunohistochemical evaluations.

Toxoplasma gondii is a protozoon parasite which causes toxoplasmosis both in human and warm-blooded animals. Toxoplasmosis is a worldwide disease and largely threats human and animal health consequently causing economic losses. Also, it affects the visceral organs in different severity degrees according to the strain of parasite and the host. In this study, experimental toxoplasmosis was performed via intra-peritoneal route in 12 gerbils by administrating 5.00 × 103 tachyzoites of T. gondii RH strain. The gerbils were sacrificed 7 days after inoculation. All systemic organs were obtained via necropsy and examined by immunohistochemical and histopathological methods. Lesions infected with T. gondii mostly observed in the serosa of abdominal cavity organs including stomach, liver, spleen, intestines, and kidneys. The lesions were most severe in liver. The parasite showed an affinity for the hepatic tissue. To our knowledge, this is the first experimental study of acute T. gondii infection in gerbil evaluating macroscopic, microscopic and immunohistochemical findings. It is concluded that Mongolian gerbils can be used as experimental animals to investigate toxoplasmosis. Also, these animals are very suitable hosts to study liver pathology and pathobiology of T. gondii-related hepatitis.

The correlation of TNF alpha levels with acute phase proteins in acute Toxoplasma gondii infection in mice.

Acute Toxoplasma gondii infections can influence the liver as well as other organs. Many cytokines and proteins play a role in the acute response against infection. Tumor necrosis factor alpha (TNF alpha) is a cytokine that plays a key function in stimulating hepatocytes to produce acute phase proteins. In this study, we investigated TNF alpha levels associated with the levels of macroglobulin, haptoglobin, hemopexin, C-reactive protein (CRP), albumin, serum amyloid alpha protein (SAA), and clusterin, which are acute phase proteins, in serum of mice with T. gondii infection. In the experiment, a total of 24 mice were used; 6 mice constituted the control group and 18 mice were infected with the RH strain. On the 2nd, 4th, and 6th days following the infection, 6 animals were euthanized, and their serums were collected. Compared to the control group, we observed a statistically significant decrease in albumin concentration in the group with T. gondii infection on the 6th day. Also, this group displayed a statistically significant, gradual increase in clusterin levels on the 2nd and 6th days, C-reactive protein levels on the 4th day, haptoglobin levels on the 2nd and 4th days, hemopexin levels on the 2nd day, serum amyloid A levels on the 2nd, 4th, and 6th days, and TNF-α levels on the 2nd, 4th, and 6th days (p < 0.05). TNF-α was strongly positively correlated with CRP, SAA, and clusterin, moderately positively correlated with hemopexin, and strongly negatively correlated with albumin. The increase in CRP, SAA, clusterin, and hemopexin levels on the 2nd day after infection, in parallel with the increase in TNF-α levels, indicates that these proteins can be considered as major acute phase proteins in acute T. gondii infection in mice. The data obtained here may be helpful for the diagnosis of T. gondii infection and for monitoring treatments.

Systolic Blood Pressure to Diastolic Blood Pressure Ratios in Diabetic and Non-diabetic Patients: Deviation from Golden Ratio.

INTRODUCTION: Cardiovascular measures like, systolic to diastolic time intervals on ECG recordings, end-diastolic to end-systolic diameters of the left ventricle on echocardiography, pulmonary and systemic hemodynamic measures have gained an interest in terms of Golden ratio or Golden proportions. Ratio of SBP to DBP as a reflection of GR has been recently evaluated in patients who have undergone ABPM to assess the presence of hypertension. AIM: To assess and compare the ratios of SBP to DBP as a reflection of GR in 24 h ABPM recordings in patients with and without DM who were not on medical treatment. METHODS: Six hundred and thirty two patients who underwent ABPM were retrospectively screened and enrolled in the study population in between October 2020 and March 2021. After exclusion of 378 who did not meet the inclusion criteria, 254 patients were enrolled in statistical analysis. Systolic blood pressure and diastolic blood pressure measurements were also averaged for the day and the night spans according to the patients' reported time of waking up and going to bed. The ABPM was programmed to measure blood pressure every 45 min during both the day time and night time periods RESULTS: Among those 254 patients included in statistical analysis, 212 patients were classified as non-diabetic and 42 patients as diabetic. SBP/DBP ratios were significantly higher in diabetics compared to those of non-diabetics in all time spans (1.698 vs 1.631, p = 0.041 for 24 h; 1.689 vs 1.618 p = 0.032 for day-time; 1.74 vs 1.66 p = 0.037 for night time). In non-diabetic patients interestingly day time SBP/DBP gave almost the same value of GR i.e 1.618, likewise the 24 h value of SBP/DBP gave the value of 1.631 which was so close to GR. On the other hand SBP/DBP ratios for all time spans were deviated far from the 1.618 in diabetic patients CONCLUSION: We have shown that systolic to diastolic blood pressure ratios of patients with DM are significantly higher than those without DM. These differences are mainly to due to the lower DBP of diabetic patients compared to non-diabetic patients. Beyond these differences SBP/DBP ratio of non-diabetic patients has shown close proximity to 1.618 known as golden ratio.

Determination of macrophage types by immunohistochemical methods in the local immune response to liver hydatid cysts in sheep.

Cystic echinococcosis is a zoonotic parasitic disease caused by Echinococcus granulosus. The main hosts in the life cycle of this parasite are dogs and other carnivores; The intermediate hosts are human, sheep, goat, cattle, pig, buffalo, horse and camel. The parasite damages the tissue by forming lesions in the form of fluid-filled cysts in the liver. These lesions are bounded by a layer of local inflammatory cells formed by the host. In the layer formed by this inflammatory response, there are lymphocytes, neutrophils and eosinophil leukocytes, including macrophages. Samples taken from sheep with hydatid cysts in their livers were followed for pathological analysis, and then histopathological and immunohistochemical examinations were performed. After histopathological examinations, the types of macrophages involved in the local immune response against cysts in the liver were determined by immunohistochemical methods using anti-INOS and anti-IL-10 antibodies. INOS and IL-10 immunopositivity were detected in all samples. Statistically, no significant difference was observed between these immunopositivity. This showed that both macrophage types are involved in the local immune response to hydatid cyst, and that Th1 and Th2 immune response stimulation continues together. It was concluded that in future studies that will be planned and experimentally, it will be possible to reveal more clearly how these macrophage types take part in the local immune response.

Assessment of venous leg symptoms in patients with hemorrhoidal disease (VEIN-HEMORRHOID study).

BACKGROUND: Coexistence of dilating venous diseases in different vascular territories has raised the idea that they have similar vascular wall abnormality in their evolutionary process. Accordingly, we aimed to evaluate venous leg symptoms in patients with hemorrhoidal disease (HD) by means of VEINES-Sym questionnaire. MATERIALS AND METHODS: The study involved 249 consecutive patients who underwent colonoscopy and met the inclusion criteria. Presence and grading of HD were made according to Goligher's classification. All patients were examined for the existing of varicose vein and classified in respect of CEAP classification. All participants were requested to answer the VEINES-Sym questionnaire. RESULTS: There was not statistically significant differences between the patients without HD (grade 0 or I) and with HD (Grade II or III) in respect to clinical characteristics except female predominance in hemorrhoid group (p = 0.07). Scores of heavy legs, swelling, burning sensation, restless leg, throbbing, tingling, and total VEINES score were significantly lower (ie: worse) in hemorrhoid group. Logistic regression analysis revealed that female gender and total VEINES score were independently associated with HD (OR: 2.03, 95% CI: 1.17-3.52, p = 0.01; OR: 0.96, 95% CI: 0.92-0.99, p = 0.02, respectively). Among all venous leg symptoms, severity of heavy legs, night cramps, swelling and aching were significantly correlated with the grades of HD. CONCLUSION: We have shown significant association between the HD and venous leg symptoms reflected by total VEINES score and significant correlation between the HD grade and venous leg symptoms severity including heavy legs, swelling, night cramps and aching legs.

Expression of serotonin 2A, 2C, 6 and 7 receptor and IL-6 mRNA in experimental toxoplasmic encephalitis in mice.

The neurotropic pathogen Toxoplasma gondii infects about one-third of the human population. Both acute and chronic (latent or life-long) forms of toxoplasmosis are associated with specific neurologic and neuropsychiatric symptoms. In the present study, swiss albino mice were inoculated intraperitoneally with 15-20 tissue cysts of the ME-49 strain of Toxoplasma gondii. The brain samples were collected on the days 10, 20, and 30 for determining the histopathological scores and the number of cysts. Furthermore, a real-time quantitative polymerase chain reaction (RT-PCR) was conducted to find out the gene expression levels of the serotonin 2A receptor (5-HTR2A), serotonin 2C receptor (5-HTR2C), serotonin 6 receptor (5-HTR6), serotonin 7 receptor (5-HTR7), and interleukin-6. The results were compared to the histopathological findings of encephalitic toxoplasmosis. The expression levels were observed to increase for all receptors; however at different time points of infection. This experimental model demonstrates that the expression of serotonin receptors was induced in Toxoplasma gondii infections, displaying unique findings for each of the individual receptors.

Role of stellate cells in hepatic echinococcosis in cattle.

Hydatid cysts formed by the metacestodes of Echinococcus granulosus. Cattle suffering from hydatid cyst shows fluid-filled structures, especially in liver. These parasite-induced cysts localized by forming fibrous capsules in the liver. Fibrogenesis is the host immune response in the liver against these parasites. Hepatic stellate cells (HSCs) are localized perisinusoidal space also known as vitamin A-storing cells, characterize the important fibrogenic cell type. In this study, livers from 15 animals with hydatid cyst and 8 healthy animals were used. Hematoxylin and Eosin, masson trichrome staining were performed on the prepared liver sections. Microscopically, cysts were bordered eosinophilic necrotic debris blended with degenerate neutrophils, macrophages, eosinophils, lymphocytes, plasma cells and multinucleated giant cells, which extend into the adjacent fibrous connective tissue. In Masson trichrome staining, the fibrous connective tissue was observed surrounding of hydatid cyst. Glial fibrillary acidic protein (GFAP), collagen I, GFAP/collagen I, positive cells were investigated using either indirect single- or double-labeling immunohistochemical staining. The results indicated that anti-GFAP-positive staining was seen in areas including fibrous tissue just under the foreign body giant cells surrounding the cyst wall. In double immunohistochemical staining, it was observed that HSCs labeled with anti-GFAP antibody in the fibrous connective tissue also labeled anti-collagen I antibody. This study shows that HSCs may responsible for synthesis the collagen I in the development of parasitic fibrosis in cystic echinococcosis in the liver of cattle.

Tracking acute phase protein response during acute and chronic Toxoplasma gondii infection.

Toxoplasmosis is a disease caused by the protozoan Toxoplasma gondii, which occurs worldwide in mammals and birds. Brain is the primary target organ because Toxoplasma gondii is a ubiquitous intracellular parasite that causes most frequently life-threatening encephalitis in immunocompromised patients. Relation of tissue cysts number, histopathology score and acute phase proteins were investigated. In this study, 36 mice are infected with Me49 strain of Toxoplasma gondii. The control group has 6 healthy mice. After inoculation of Toxoplasma gondii, at 10., 15., 20., 30., 45., 60. days, 6 each mice euthanized after collection of blood samples. Hemopexin, haptoglobulin, macroglobulin, serum amyloid A and clusterin levels are determined by ELISA. Then, brain tissues were investigated histopathologically and lesions were scored. The average cyst numbers were determined by counting three samples (25 µl each) of each brain homogenate under light microscopy. Inflammatory reaction was observed on day 10 days after inoculation (d.a.i.) The lesions were characterized by perivascular mononuclear cell infiltration, focal mononuclear cell infiltration in the meninges, and glial proliferation. Tissue cysts were observed in all Toxoplasma gondii-infected groups. The highest lesion score was observed at 60 d.a.i. And the most tissue cyst number were on day 30. d.a.i. Serum levels of hemopexin, haptoglobulin, macroglobulin, serum amyloid A and clusterin were significantly higher than the control group on day 10-20., 10., 10-30., 10.,10-45 d.a.i., respectively. High level of acute phase proteins in mice on certain days infected with Toxoplasma gondii was exhibited a relationship between brain lesions and tissue cysts.

Comparison of the clinical, radiographic, and histological effects of titanium-prepared platelet rich fibrin to allograft materials in sinus-lifting procedures.

AIM: In the present study, we evaluated the clinical, radiographic, and histological comparisons of completely autologous titanium-prepared platelet rich fibrin (T-PRF) or allograft in sinus-lifting procedures. METHODS: Eighteen posterior maxilla requiring sinus-lifting procedures using the balloon-lifting technique for implant placement were selected. Ten sinuses were randomly assigned to T-PRF as the test group and eight to allografts as the control group. After 4 and 6 months in the test and control groups, respectively, computed tomography was done, and bone samples were received during implant surgery. Three months after the second surgery, implant stability was measured. RESULTS: Radiological results showed that the allograft group had better results (62% in volume, 53% in density, and 69% in height) than the T-PRF group. Histomorphometric results showed that newly-formed bone ratios were 17.28 ± 2.53 and 16.58 ± 1.05 in the allograft group and T-PRF groups, respectively. There was no significant difference between the test and control groups (P = .611) for implant stability values. CONCLUSIONS: The use of T-PRF alone in sinus-lifting operations has successful clinical and histomorphometric results. Bone formation in the T-PRF group was accelerated to 4 months compared to allografts according to the histological results.

Paracetamol-induced nephrotoxicity and oxidative stress in rats: the protective role of Nigella sativa.

Context Nigella sativa L. (Ranunculaceae) (NS) is traditionally used to treat many conditions such as inflammation. Objective This study evaluates the effects of NS seeds ethanol extract in paracetamol-induced acute nephrotoxicity in rats. Materials and methods Forty-eight female Wistar Albino rats were divided into eight groups: I = sham; II = sham + 1000 mg/kg NS; III = sham + 140 mg/kg (N-acetyl cysteine) NAC; IV = 2 g/kg paracetamol; V = 2 g/kg paracetamol + 140 mg/kg NAC; VI, VII and VIII = 2 g/kg paracetamol + 250, 500 and 1000 mg/kg NS, respectively. Paracetamol administration (oral) was carried out 1 h after NS and NAC administrations (oral), and all animals were sacrificed 24 h later. Results Paracetamol administration significantly increased serum urea (88.05 U/L) and creatinine (0.80 U/L) when compared with the sham group (49.80 and 0.31 U/L, respectively). However, serum urea level was reduced to 65.60, 56.00 and 54.18 U/L, with 250, 500 and 1000 mg/kg doses of the extract, respectively. Also, serum creatinine level was reduced to 0.64, 0.57 and 0.52 U/L with 250, 500 and 1000 mg/kg doses of the extract, respectively. NS administration increased superoxide dismutase and glutathione, and decreased malondialdehyde levels in the kidneys. Kidney histopathological examinations showed that NS administration antagonized paracetamol-induced kidney pathological damage. Discussion and conclusions The results suggest NS has a significant nephroprotective activity on paracetamol-induced nephrotoxicity. It may be suggested that the antiinflammatory and antioxidant effects of NS ethanolic extract originated from different compounds of its black seeds.

Role of oxidative stress in the pathophysiology of Toxoplasma gondii infection.

Oxidative stress (OS) plays an essential role in the pathogenesis of common neurodegenerative diseases. We have previously shown that Toxoplasma gondii (T. gondii) induces high nitric oxide (NO) production, glial activation, and apoptosis that altogether cause severe neuropathology in toxoplasma encephalitis (TE). The objective of this study was to investigate the cytotoxic effect of OS and to identify a correlation between the causes of T. gondii induced neuropathology. Expression levels of glutathione reductase (GR), Cu/Zn superoxide dismutase (SOD1), neuron specific enolase (NSE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were investigated. Results of the study revealed that the levels of GR (P <0.005) and NSE (P <0.001) expression in the brain tissue markedly increased while SOD1 activity decreased (P <0.001) in the infected group compared to the non-infected group. In addition, intense staining for 8-OHdG (P <0.05) was observed both in the nucleus and the cytoplasm of neurons and glial cells that underwent OS. These results were reasonable to suggest that T. gondii-mediated OS might play a pivotal role and a different type of role in the mechanism of neurodegeneration/neuropathology in the process of TE. The results also clearly indicated that increased levels of NO and apoptosis might contribute to OS-related pathogenesis of TE. As a result, OS and expression of NSE might give an idea of the disease progress and may have a critical diagnostic significance for patients with T. gondii infection.

Increased expressions of ADAMTS-13 and apoptosis contribute to neuropathology during Toxoplasma gondii encephalitis in mice.

Toxoplasma gondii (T. gondii) is a protozoan parasite with the potential of causing severe encephalitis among immunocompromised humans and animals. Our previous study showed that T. gondii induces high nitric oxide (NO) production, high glial activation (GFAP) and neurofilament expressions, leading to severe neurodegeneration in toxoplasma encephalitis (TE) in the central nervous system (CNS). The aim of this experimental study was to investigate ADAMTS-13 expression and apoptosis in CNS and to identify whether they have any correlation with toxoplasmosis neuropathology and neurodegeneration. Mice were infected with ME49 strain T. gondii and the levels of ADAMTS-13, caspase 3, caspase 8, caspase 9, TNFR1 and Bcl-xL expressions were examined in brain tissues by immunohistochemistry, during the development and establishment of chronic infections at 10, 30 and 60 days post-infection. Results of the study revealed that the levels of ADAMTS-13 (P < 0.005), caspase 3 (P < 0.05), caspase 8 (P < 0.05), caspase 9 (P < 0.005) and TNFR1 (P < 0.05) expressions in the brain markedly increased while Bcl-xL expression decreased (P < 0.005). The most prominent finding from our study was that 10, 30 and 60 days post-infection ADAMTS-13 increased significantly and this may play an important role in the regulation and protection of the blood-brain barrier integrity and CNS microenvironment in TE. These results also suggest that T. gondii-mediated apoptosis might play a pivotal role and a different type of role in the mechanism of neurodegeneration and neuropathology in the process of TE. Furthermore, expression of ADAMTS-13 might give an idea of the progress and is critical for diagnosis of this disease. To the best of the authors' knowledge, this is the first report on ADAMTS-13 expression in the CNS of T. gondii-infected mice.