Betatrophin, elabela, asprosin, glucagon and subfatin peptides in breast tissue, blood and milk in gestational diabetes.

We investigated the presence of asprosin (ASP), betatrophin, elabela (ELA), glucagon and subfatin (SUB) in the milk of mothers with gestational diabetes mellitus (GDM) and compared their levels with blood levels. We also investigated whether these peptides are synthesized by the breast. We investigated 12 volunteer mothers with GDM and 14 pregnant non-GDM control mothers. The peptides were measured using ELISA and their tissue localization was determined using immunohistochemistry. Breast milk contains ASP, betatrophin, ELA, glucagon and SUB. The amount of the peptides ranged from highest to the lowest in colostrum, transitional milk and mature milk. The amount of peptides in the milk was greater than for blood. The peptides, except for ELA, were increased in milk and blood by GDM. Betatrophin and ELA are synthesized in the connective tissue of the breast. ASP, glucagon and SUB are synthesized in the alveolar tissue of the breast. These peptides in breast milk may contribute to the development of the gastrointestinal tract of newborns and infants.

Subfatin and asprosin, two new metabolic players of polycystic ovary syndrome.

Asprosin and subfatin are recently discovered two new hormones of adipocyte origin that play a role in the regulation of glucose metabolism. Polycystic ovary syndrome (PCOS) is a gynaecological syndrome presenting with energy turbulence. The aim of this study was to investigate whether asprosin and subfatin play a role in PCOS disease. Thirty participants with a diagnosis of PCOS and thirty control group participants were included in this case-control study. Hormone profiles of the participants (subfatin, asprosin, insulin, prolactin, thyroid-stimulating hormone (TSH), oestradiol (E2), follicle-stimulating hormone (FSH), luteinising hormone (LH), dehydroepiandrosterone sulphate (DHEA-SO4), lipid profiles [(total testosterone, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride, cholesterol)], fasting blood sugar (FBS) and high-sensitivity C-reactive protein (hs-CRP) values were measured. While the levels of asprosin, LDL and triglyceride, TSH, E2, FSH, LH, DHEA-SO4 were found to be significantly higher in patients with PCOS compared to controls (p = .005; p = .01), subfatin and HDL levels were found to be low. Significantly decreasing subfatin and increasing asprosin levels in circulation in PCOS may play a role in the etiopathology of this disease and that they may also be new candidate molecules in addition to classical laboratory parameters in the diagnosis and follow-up of PCOS in the future.Impact statementWhat is already known on this subject? The studies investigating the relationship between PCOS and asprosin are contradictory. Although subfatin has been studied in many metabolic diseases, it has not been studied yet whether it is associated with PCOS. Furthermore, whether there is a mutual relationship between subfatin and asprosin in patients with PCOS has not been studied yet.What do the results of this study add? This available data indicates that significantly decreasing subfatin and increasing asprosin levels in the circulation in PCOS may play a role in the etiopathology of this disease.What are the implications of these findings for clinical practice and/or further research? The findings are promising in that decreasing subfatin and increasing asprosin levels will shed new light on reproductive endocrinology changes caused by PCOS and may help to clarify the pathophysiology of PCOS. Furthermore, in our study, the asprosin/subfatin ratio was above three in PCOS disease. This ratio reported here is anticipated to contribute to the course or follow-up of the disease in the future. Also, subfatin has been investigated here for the first time, may also be a new candidate molecule in addition to classical laboratory parameters in the diagnosis and follow-up of PCOS.

Asprosin in umbilical cord of newborns and maternal blood of gestational diabetes, preeclampsia, severe preeclampsia, intrauterine growth retardation and macrosemic fetus.

Pathological pregnancies, such as gestational diabetes, preeclampsia, severe preeclampsia, intrauterine growth retardation and macrosomic fetuses, are among the most fundamental problems of obstetrics clinics that are risk factors for both mother and child. Our main goal here is to compare maternal blood and newborn venous-arterial cord blood asprosin levels in pathological and healthy pregnancies. The study included 30 pregnant women with gestational diabetes, 30 with preeclampsia, 30 with severe preeclampsia, 30 with intrauterine growth retardation, 29 with macrosomic fetuses and 30 healthy pregnant women. All mothers were voluntary participants. Arteries and venous blood samples from both mothers and newborns were taken, in which asprosin levels were measured by ELISA. There was a statistically significant increase in asprosin levels in pregnant women with gestational diabetes, preeclampsia, severe preeclampsia and macrosemic fetuses compared with the control group, whereas in those with intrauterine growth retardation a significant decrease was observed. Venous and arterial cord blood asprosin levels were also close to maternal asprosin levels. Regarding the asprosin levels in venous and arterial cord blood in all newborns, the former was higher, but was not statistically significant.

Evaluation of elabela, apelin and nitric oxide findings in maternal blood of normal pregnant women, pregnant women with pre-eclampsia, severe pre-eclampsia and umbilical arteries and venules of newborns.

Pre-eclampsia is multisystem metabolic diseases, commonly accompanied by hypertension and proteinuria, which are among the important causes of maternal and perinatal mortality and morbidity worldwide. In a pre-eclampsia animal model study in the last year, Elabela (ELA) infusion was reported to correct hypertension and proteinuria and to normalise the birth weights of the offspring. Therefore, our main goal in this human study is to compare ELA, apelin (APLN) and nitric oxide (NO) levels in the maternal blood of pregnant women with pre-eclampsia and severe pre-eclampsia and in their newborns' venous-arterial cord blood with maternal blood of healthy pregnant women and their newborns' venous-arterial cord blood. Thirty controls, 28 pre-eclampsia and 24 severe pre-eclampsia cases and their newborns participated in this study. Maternal blood and newborn venous-arterial cord blood samples were collected from these patients. ELA, APLN and NO levels in these samples were measured by ELISA method. When the maternal blood ELA, APLN and NO amounts were compared with control groups, there was a significant decrease in both pre-eclamptic and severe pre-eclamptic women and this was more prominent in the women with severe pre-eclampsia. When ELA, APLN and NO levels in the newborn venous-arterial cord blood of control group was compared with that of severe pre-eclamptic and pre-eclamptic women; it was parallel with maternal findings. ELA, APLN and NO levels appear to play a role in the pathophysiology of pre-eclampsia. It is predicted that if these molecules, which are reduced due to pre-eclampsia and severe pre-eclampsia, are brought to physiological limits in the future; pre-eclampsia related maternal and perinatal mortality and morbidity can be reduced. Impact Statement What is already known on this subject? There are two studies (one human and one animal) in the literature evaluating only maternal elabela (ELA) levels in pre-eclamptic pregnancies. The animal study demonstrated decreased blood ELA levels in pre-eclamptic animals and the human study found increased blood ELA levels in pre-eclamptic patients. There are no studies evaluating maternal ELA levels in severe pre-eclampsia patients and also there are no studies evaluating maternal ELA levels in pre-eclampsia and severe pre-eclampsia patients. There are no studies evaluating newborns' venous-arterial blood APLN and NO levels. Apelin (APLN) and nitric oxide (NO) results were controversial in pre-eclampsia and severe pre-eclampsia patients. What the results of this study add? The present study, for the first time, demonstrates that decreased blood ELA, APLN and NO levels in maternal blood of pregnant women with pre-eclampsia and severe pre-eclampsia and in their newborns' venous-arterial blood. Furthermore, we have also demonstrated for the first time that decreased ELA, APLN and NO are also related with low birth weights. What the implications are of these findings for clinical practice and/or further research? The low levels of ELA, APLN and NO in maternal blood and newborns' venous-arterial blood may be the result or the cause of pathologic changes in pre-eclampsia and severe pre-eclampsia. Also, ELA, APLN and NO may be new indicator parameters of systemic endothelial dysfunction together. More studies are needed to evaluate the relationship between of ELA, APLN and NO and pre-eclampsia and severe pre-eclampsia and in newborns' venous-arterial blood.

Chemerin and Dermcidin in Human Milk and Their Alteration in Gestational Diabetes.

BACKGROUND: Chemerin and dermcidin, which have antimicrobial properties, are molecules that are also related to insulin resistance and inflammation. RESEARCH AIMS: The aims were to determine the amounts of chemerin and dermcidin in the milk and blood of mothers with gestational diabetes, and to compare the amounts of chemerin and dermcidin in the milk and blood of mothers with and without diabetes. METHODS: This was a two-group nonrandomized longitudinal study with a convenience sampling of mothers without gestational diabetes (n = 27) and mothers with gestational diabetes (n = 26). Human milk and blood samples were obtained from these mothers during colostrum, transitional, and mature milk periods. The amount of chemerin and dermcidin in these samples was measured by enzyme-linked immunosorbent assay. RESULTS: The presence of chemerin and dermcidin was first detected in human milk. The amounts of chemerin and dermcidin in the blood of all the mothers were greater in the colostrum period and lowest in the mature period. The amount of chemerin and dermcidin in the milk of all the mothers was greater than that in the blood. The amounts of chemerin and dermcidin were significantly increased in both blood and human milk within the gestational age samples. CONCLUSIONS: Chemerin and dermcidin may contribute to the protection of infants from infections during infancy. Increased amounts of these molecules found within the gestational diabetes group may also prevent adverse maternal and fetal outcomes.

COULD OZONE TREATMENT BE A PROMISING ALTERNATIVE FOR OSTEOMYELITIS? AN EXPERIMENTAL STUDY.

OBJECTIVE: The aim of the present study was to investigate the biochemical and histopathological impact of ozone treatment in an experimental model of osteomyelitis in rats. METHODS: A total of 24 adult male Sprague-Dawley rats (3 months old, each weighing 300 to 400 g) were randomly allocated into three groups. Group I (n=8) served as a control and received no interventions or medications. In Group II (n=8), osteomyelitis was induced in the femur and no treatment was applied. Group III (n=8) received intraperitoneal ozone treatment for 3 weeks after the formation of osteomyelitis in the femur. Serum samples were taken to assess total antioxidant capacity (TAC), protein carbonyl content (PCO), and lactate dehydrogenase (LDH). Bone specimens obtained from the femur were histopathologically evaluated for inflammation, necrosis, osteomyelitis, and abscess formation. RESULTS: Serum TAC levels were notably higher (p<0.001), while LDH levels were lower (p=0.002) in Group III than Group II. No significant difference was detected between groups with respect to PCO level. Similarly, Group III displayed more favorable histopathological outcomes with respect to osteomyelitis (p=0.008), inflammation (p=0.001), necrosis (p=0.022), and abscess formation (p=0.022). CONCLUSION: Ozone may be a useful adjunct treatment for osteomyelitis. Further studies in animals and humans are needed to clarify and confirm these preventive effects, understand the underlying pathophysiology, and establish guidelines. Level of Evidence II; Prospective comparative study.

OBJETIVO: O objetivo do presente estudo foi investigar o impacto bioquímico e histopatológico do tratamento de ozônio em modelo experimental de osteomielite em ratos. MÉTODOS: Vinte e quatro ratos Sprague-Dawley machos adultos (3 meses de idade, pesando de 300 a 400 g) foram alocados randomicamente em três grupos. O grupo I (n = 8) serviu como controle. No Grupo II (n = 8), o modelo de osteomielite experimental foi induzido no fêmur e não foi aplicado nenhum tratamento. O grupo III (n = 8) recebeu tratamento com ozônio intraperitoneal por 3 semanas depois da formação de osteomielite no fêmur. Foram coletadas amostras de sangue para avaliar a capacidade antioxidante total (CAT), a concentração da proteína carbonil (PCO) e da lactato desidrogenase (LDH) no soro. As amostras do fêmur foram avaliadas por histopatologia quanto a inflamação, necrose, osteomielite e formação de abscesso. RESULTADOS: Os níveis séricos de TAC foram notavelmente maiores (p < 0,001), enquanto os níveis de LDH foram menores (p = 0,002) no Grupo III em comparação com o Grupo II. Nenhuma diferença significativa foi detectada entre os grupos com relação ao nível de PCO. Do mesmo modo, o Grupo III apresentou resultados histopatológicos mais favoráveis para osteomielite (p = 0,008), inflamação (p = 0,001), necrose (p = 0,022) e formação de abscesso (p = 0,022). CONCLUSÃO: O ozônio pode ser um tratamento adjuvante útil na osteomielite. Mais estudos com animais e com seres humanos são necessários para esclarecer e confirmar esses efeitos preventivos, compreender a fisiopatologia subjacente e estabelecer diretrizes. Nível de Evidência II; Estudo prospectivo comparativo.

An experimental study on the preventive effects of N-acetyl cysteine and ozone treatment against contrast-induced nephropathy.

PURPOSE: To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. METHODS: Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. RESULTS: Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. CONCLUSION: The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.

An experimental study on the preventive effects of N-acetyl cysteine and ozone treatment against contrast-induced nephropathy

Abstract Purpose: To compare the preventive effects of N-acetyl cysteine (NAC), ozone preconditioning and ozone treatment against contrast-induced nephropathy (CIN) in an experimental rat model. Methods: Thirty adult male Wistar rats were randomly distributed into five groups (n=6 for each group). Group I served as control and Group II had only contrast agent, while Group III received NAC and Group IV received intraperitoneal ozone 6 hours before and 6 hours after introduction of contrast agent. Ozone treatment was applied for 5 days after the contrast agent was introduced in Group V. After induction of CIN, groups were compared in terms of serum levels of urea, creatinine, neutrophil gelatinase associated lipocalin, protein carbonyl, total antioxidant capacity (TAC) as well as degree of renal injury at histopathologic level. Results: Groups II-V displayed more obvious histopathological alterations such as hemorrhage and renal tubular injury compared with Group I. TAC (p=0.043) and creatinine (p=0.046) levels increased significantly in Group II after the intervention. In Group III, protein carbonyl level diminished remarkably (p=0.046), while creatinine level was increased (p=0.046) following the intervention. TAC level was higher in Group IV (p=0.028) and Group V (p=0.026) following the procedure. Conclusion: The N-acetyl cysteine and ozone treatment may alleviate the biochemical and histopathological deleterious effects of contrast-induced nephropathy via enhancement of total antioxidant capacity and decreasing oxidative stress.

The beneficial effects of ozone therapy in acetaminophen-induced hepatotoxicity in mice.

BACKGROUND: The aim of the present study was to determine the therapeutic effects of medical ozone therapy on acute acetaminophen (APAP)-induced hepatotoxicity which were not clearly demonstrated in prior studies. METHOD: Twenty-four mice were randomly assigned into three equal groups: Group 1 (control), Group 2 (APAP) and Group 3 (APAP +ozone). Hepatotoxicity was induced by APAP given as a single dose of 300mg/kg intraperitoneally in Groups 2 and 3. Additionally, Group 3 received 20mcg/0.5mL ozone intraperitoneal twice a day for the remaining of the study. Other groups received saline injections. On the fourth day of the study, biochemical variables (AST, ALT, ALP) and liver histopathology was assessed. RESULTS: Intraperitoneal administration of a single dose of APAP induced hepatocellular damage that was shown by both liver enzymes and histopathological changes (p<0.001). AST, ALT, ALP levels were elevated in both groups 2 and 3 and the difference from group 1 was statistically significant (p<0.01).Mean ALT and AST levels of group 2 were statistically significantly higher versus group 3 (p<0.01). In histopathological examinations; necrosis and inflammation were more prominent in Group 2 compared to Group 3 (p<0.01). CONCLUSION: Ozone showed beneficial effects on APAP hepatotoxicity at a statistically significant level. It is known that ozone has therapeutic effects in various diseases owing to its antioxidant effects. The present study suggests that ozone may be utilized as a routine supplementary therapy in acute APAP hepatotoxicity.

Could ozone treatment be a promising alternative for osteomyelitis? an experimental study / O tratamento com ozônio pode ser uma alternativa promissora para a osteomielite? um estudo experimental

ABSTRACT Objective: The aim of the present study was to investigate the biochemical and histopathological impact of ozone treatment in an experimental model of osteomyelitis in rats. Methods: A total of 24 adult male Sprague-Dawley rats (3 months old, each weighing 300 to 400 g) were randomly allocated into three groups. Group I (n=8) served as a control and received no interventions or medications. In Group II (n=8), osteomyelitis was induced in the femur and no treatment was applied. Group III (n=8) received intraperitoneal ozone treatment for 3 weeks after the formation of osteomyelitis in the femur. Serum samples were taken to assess total antioxidant capacity (TAC), protein carbonyl content (PCO), and lactate dehydrogenase (LDH). Bone specimens obtained from the femur were histopathologically evaluated for inflammation, necrosis, osteomyelitis, and abscess formation. Results: Serum TAC levels were notably higher (p<0.001), while LDH levels were lower (p=0.002) in Group III than Group II. No significant difference was detected between groups with respect to PCO level. Similarly, Group III displayed more favorable histopathological outcomes with respect to osteomyelitis (p=0.008), inflammation (p=0.001), necrosis (p=0.022), and abscess formation (p=0.022). Conclusion: Ozone may be a useful adjunct treatment for osteomyelitis. Further studies in animals and humans are needed to clarify and confirm these preventive effects, understand the underlying pathophysiology, and establish guidelines. Level of Evidence II; Prospective comparative study.

RESUMO Objetivo: O objetivo do presente estudo foi investigar o impacto bioquímico e histopatológico do tratamento de ozônio em modelo experimental de osteomielite em ratos. Métodos: Vinte e quatro ratos Sprague-Dawley machos adultos (3 meses de idade, pesando de 300 a 400 g) foram alocados randomicamente em três grupos. O grupo I (n = 8) serviu como controle. No Grupo II (n = 8), o modelo de osteomielite experimental foi induzido no fêmur e não foi aplicado nenhum tratamento. O grupo III (n = 8) recebeu tratamento com ozônio intraperitoneal por 3 semanas depois da formação de osteomielite no fêmur. Foram coletadas amostras de sangue para avaliar a capacidade antioxidante total (CAT), a concentração da proteína carbonil (PCO) e da lactato desidrogenase (LDH) no soro. As amostras do fêmur foram avaliadas por histopatologia quanto a inflamação, necrose, osteomielite e formação de abscesso. Resultados: Os níveis séricos de TAC foram notavelmente maiores (p < 0,001), enquanto os níveis de LDH foram menores (p = 0,002) no Grupo III em comparação com o Grupo II. Nenhuma diferença significativa foi detectada entre os grupos com relação ao nível de PCO. Do mesmo modo, o Grupo III apresentou resultados histopatológicos mais favoráveis para osteomielite (p = 0,008), inflamação (p = 0,001), necrose (p = 0,022) e formação de abscesso (p = 0,022). Conclusão: O ozônio pode ser um tratamento adjuvante útil na osteomielite. Mais estudos com animais e com seres humanos são necessários para esclarecer e confirmar esses efeitos preventivos, compreender a fisiopatologia subjacente e estabelecer diretrizes. Nível de Evidência II; Estudo prospectivo comparativo.

An experimental study of ascorbic acid effects in acute renal failure under general anesthesia.

PURPOSE: To evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model. METHODS: Twenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg/kg) and high (300 mg/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation. RESULTS: NGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p<0.001) and cast (p<0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III. CONCLUSIONS: The ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.

An experimental study of ascorbic acid effects in acute renal failure under general anesthesia

Abstract Purpose: To evaluate the preventive effect of ascorbic acid on sevoflurane-induced acute renal failure in an experimental rat model. Methods: Twenty-four adult male Wistar rats were randomly distributed into three groups. Subjects were allocated into 3 groups: Group I received sevoflurane only, whereas Groups II and III had moderate (150 mg/kg) and high (300 mg/kg) doses of AA in addition to sevoflurane, respectively. Rhabdomyolysis and myohemoglobinuric ARF was formed by intramuscular administration of glycerol on the upper hind limb on the 15th minute of inhalation anesthesia. Biochemical parameters consisted of serum levels of blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin (NGAL), total antioxidant capacity (TAC), and protein carbonyl content. Histopathological variables were tubular necrosis, fibrin, and cast formation. Results: NGAL levels were significantly lower in Group III than Group II and Group I. On the other hand, TAC, PCO, urea and creatinine levels were notably higher in Group I compared with Groups II and III. There was a significant difference between 3 groups on frequencies of acute tubular necrosis (p=0.003), fibrin (p<0.001) and cast (p<0.001). Acute tubular necrosis and fibrin formation were more prominent in Group I. Casts were more common in Groups II and III. Conclusions: The ascorbic acid serve as a prophylactic agent against renal damage in patients receiving sevoflurane anesthesia and higher doses were associated with more apparent protective effects.