Introduction: Metformin-associated Lactic acidosis is a rare, yet fatal condition, especially in the presence of risk factors. Therapeutic use of metformin may induce Lactic acidosis. Gastrointestinal bleeding, dehydration, acute renal failure, and drugs are major risk factors that increase the mortality risk associated with metformin-associated Lactic acidosis. In this regard, this case study aimed to present a patient, who died due to metformin-associated Lactic acidosis despite treatment. Method: This case study featured a 45-year-old diabetic patient with metformin use, who presented to the emergency department with the complaint of low back pain. He had acute renal failure, severe Lactic acidosis, and shock findings. Discussion: The primary purpose of metformin-associated Lactic acidosis treatment is to restore acid-base balance and provide hemodynamic support. Hemodialysis reduces the mortality due to metformin-associated Lactic acidosis by decreasing lactate clearance. Supportive therapies should be used. Nevertheless, mortality still occurs in approximately 50% of the cases. Conclusion: Metformin overdose or even therapeutic levels of metformin use can cause MALA in the presence of various risk factors. MALA, a rare clinical condition, is associated with mortality rates of up to 50%. The most crucial step in treating MALA is hemodialysis/venous hemofiltration. Given that metformin is a frequently used medication, care should be taken in the follow-up of patients using metformin, considering MALA.

Background: Mitochondrial myopathy, encephalopathy, Lactic acidosis and stroke-like episodes (MELAS) is a progressive maternally inherited multi-organ disorder caused by a mutation in a mitochondrial gene. In this disorder recurrent migraine headache, seizure, cerebral insults causing hemiparesis, hemianopia, progressive hearing loss and cognitive problems may occur.Case presentation: The patient is a 12-year girl manifested with malaise, tonic-clonic convulsion and unilateral weakness in left upper and lower extremities. Her problem was begun with seizure, headache and recurrent vomiting, 5 months before the admission. On clinical examination cerebrovascular events was diagnosed. On broader diagnostic studies, also a genetic mutation in A3243G gene, as a definite characteristic for the establishment of the disease, was detected by muscle biopsy.Conclusion: Patients suffering from the syndrome gradually display delayed motor and cognitive development. Therapeutic management of the disease consists of administration of multi-vitamins and coenzyme supplementations, and lowering the serum lactate level using dichloroacetate.

For induction of ruminal acidosis, 10 clinically healthy three years old non pregnant female sheep were selected. Prior to the infusion of sucrose (0 hour), rumen and blood samples were obtained in order to determine baseline rumen and blood pH, respectively. Electrocardiogram (ECG) was also recorded. Acute ruminal acidosis was induced experimentally with sucrose at a dose of 18g kg-1 body weigh through rumen fistula. ECG was recorded and blood and rumen samples collected at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36, and 48 hours after the infusion of sucrose. Results indicated that blood and rumen pH decreased significantly at 15, 18, 21, 24, 30, 36 and 48 hours and at 3, 6, 9, 12, 15, 18, 21, 24, 30, 36 and 48 hours, respectively. acidosis produced a marked increasing in heart rate and a decrease in PR interval at 15 and 18 hour significantly with little apparent effect on the ST and PR segment. The P amplitude increased significantly at 6, 9, 12, 15, 18, 21, 24 and 30 hours. The T amplitude increased significantly at 9, 12, 15, 18, 21, 24, 30 and 36 hours. The RR interval decreased significantly at 6, 9, 12, 15, 18, 21, 24, 30, 36 and 48 hours. In conclusion acute ruminal acidosis caused significant changes in ECG of sheep though there was not any detectable arrhythmia in the ECG in acute ruminal acidosis.

Objective(s): Causality of occurrence of metformin-associated Lactic acidosis (MALA) is a clinical problem. Currently, there is no drug available to prevent MALA. The present study was conducted to evaluate the protective effect of Berberine (BBR) against MALA in induced diabetic rat model. Materials and Methods: A sample of 75 healthy male Wistar rats was randomly selected according to inclusion and exclusion criteria. 75 male Wistar rats were randomly divided into a control and 4 experimental groups. Streptozotocin (STZ) in citrate buffer (pH 4. 5) at a dose of 45 mg/kg was injected for induction of diabetes mellitus and rats achieving fasting blood glucose >250 mg/dl were included. Blood samples were collected 18 hr after the last dose of metformin and berberine. Ethical approval was taken before the study was conducted. Staistix 10. 0 (USA) software was used for data analysis. Results: Berberine decreased MALA. Metformin, metformin + BBR 50 mg/kg bwt, and metformin + BBR 100 mg/kg bwt showed serum lactate as 1. 87± 0. 4 mmol/lL, 1. 62 ± 0. 44 mmol/l and 1. 47± 0. 45 mmol/l, respectively (P=0. 0001). Insulin resistance and liver enzymes were improved in BBR treated rats. Conclusion: The present study reports berberine protects against MALA in streptozocin-induced diabetes mellitus.

Rumen Lactic acidosis is a metabolic disorder which develops in ruminants that have ingested large amounts of unaccustomed feeds rich in ruminally fermentable carbohydrates. In this study we investigated the relationship between serum lactate levels and ruminal fluid pH with changes of cardiac damage biomarkers in serum in 200 sheep with acute ruminal Lactic acidosis (ARLA) and 50 healthy ones. After confirmation of ARLA through clinical examination and ruminal fluid pH5.5, venous blood samples were collected and special analysis carried out on serum samples. According to the findings ruminal fluid pH in diseased and healthy sheep were 5.28 ± 0.2 and 6.93±0.3, respectively. Serum lactate level in sheep with ARLA was significantly higher than normal sheep. (p=0.000). cTnI levels was 0.684±0.03 ng/ml in sheep with ARLA, which was significantly (p=0.000) higher than healthy sheep (0.005±0.00 ng/ml). Other cardiac biomarkers were increased in diseased group, however only elevation of serum activities of AST and CK-MB were statistically significant (p=0.002 and p=0.007 respectively). Although serum LDH activity in diseased group was higher than control group; but this difference was statistically non-significant (p=0.063). There was significant negative correlation between ruminal fluid pH with cTnI concentrations (p=0.004; r=–0.850); so that highest levels of cTnI (2.28 to 3.06 ng/ml) were recorded in three sheep with ruminal fluid pH<4.5. Despite medical treatments, all of these sheep died. Increase of serum activities of cardiac enzymes and cTnI concentration in sheep affected by ARLA without cardiac disease may be due to indirect effects of acidosis on cardiac muscle mediated by metabolic changes, tachycardia and increasing of sympathetic tone. In conclusion, the significant correlations observed between serum lactate level and cardiac biomarkers could be due to alterations in cardiac muscle function brought about by this metabolic disease.

Introduction. Metformin-associated Lactic acidosis is rare despite its widespread use. It is often associated with the use of metformin in the presence of chronic kidney disease, but it may also occur in people with normal renal function in the case of acute overdose. Case Report. 20 years old (patient 1) and 37 years old (patient 2) women without any chronic disease took 40 gram (727 mg/ kg) and 60 gram (1200 mg/kg) metformin, respectively; for the suicidal attempt. Deep Lactic acidosis was detected in patients. In patient 1, hemodialysis was performed for 4 hours. After the interruption, deep acidosis evolved again and another dialysis session was performed. In patient 2, hemodialysis was performed for 16 hours without any interruption and she did not need any other dialysis session. Conclusion. Metformin has a large distribution volume. It is not correct to make a final decision as to how long the dialysis will continue when dialysis begins. Dialysis should be continued without interruption until clinical and laboratory targets are achieved.

Background: Identifying the effective factors in the progression toward Lactic acidosis and death is essential in improving the treatment of Metformin-poisoned patients. This study investigates the blood lactate level in Metformin-poisoned patients and the factors affecting it.Methods: This was a case series study in two referral clinical toxicology centers in Iran for one year. 16 patients were included in the study. The questionnaire was filled out based on the demographic characteristics of the person, vital signs, poisoning symptoms, blood biochemistry, blood gases, blood sugar, and treatments. The lactate level was measured 6-12-24 hours later.Findings: Three cases (18.8%) were male and 13 (81.3%) were female. The average age was 30.13 ± 16.22 years. One case of hypoglycemia, three cases of metabolic acidosis, and three cases of creatinine level above 1.2 were observed. The initial pH and bicarbonate were predictors of the lactate level. No cases of death or Lactic acidosis were observed.Conclusion: Blood pH and bicarbonate can be used as predictors of serum lactate increase. Also, this study showed that the probability of death and Lactic acidosis with metformin is very low.

Patients with mitochondrial encephalopathy, Lactic acidosis and stroke-like episodes (MELAS) present with recurrent and partially reversible neurological deficits. Lesions of MELAS classically cause a signal change in both the grey and white matter, predominantly in the occipital and parietal lobes. These lesions mimic infarction. Here, we reported a case of MELAS with rare neuroimaging finding of hemispheric cortical thickening on T2/FLAIR images with intracortical nodular gadolinium enhancement; then we discussed the clinical and radiological differential diagnoses of it.