LOW LEVELS OF SERUM CYANOCOBALAMIN IN A METFORMIN-TREATED PATIENT. CASE REPORT AND COMPARISON WITH LITERATURE DATA.

Metformin is a widely used oral antidiabetic biguanide compound. According to the literature, metformin may lower the serum cyanocobalamin levels. We present the case of a 71-old-male treated with metformin for 15 years. When presenting to a periodic checkup, low serum cyanocobalamin levels where found. Laboratory tests showed levels below normal range for hemoglobin (12.7 g/dL) and hematocrit (37.8%). After patient reevaluation, a change in antidiabetic treatment will be considered if metformin will be found the cause of low serum cyanocobalamin levels. Other cases reported in the literature support this hypothesis, justifying the study of the influence of metformin therapy on serum vitamin B12 levels in patients diagnosed with diabetes. The influence of patient age, metformin dosage, duration of treatment and time since diabetes diagnosis on serum levels of vitamin B12 also need to be determined.

FIXED DOSE COMBINATIONS WITH SELECTIVE BETA-BLOCKERS: QUANTITATIVE DETERMINATION IN BIOLOGICAL FLUIDS.

Hypertension is one of the most common causes of death, a complex and incompletely controlled disease for millions of patients. Metoprolol, bisoprolol, nebivolol and atenolol are selective beta-blockers frequently used in the management of arterial hypertension, alone or in fixed combination with other substances. This study presents the most used analytical methods for simultaneous determination in biological fluids of fixed combinations containing selective beta-blockers. Articles in Pub-Med, Science Direct and Wiley Journals databases published between years 2004-2014 were reviewed. Methods such as liquid chromatography--mass spectrometry--mass spectrometry (LC-MS/MS), high performance liquid chromatography (HPLC) or high performance liquid chromatography--mass spectrometry (HPLC-MS) were used for determination of fixed combination with beta-blockers in human plasma, rat plasma and human breast milk. LC-MS/MS method was used for simultaneous determination of fixed combinations of metoprolol with simvastatin, hydrochlorothiazide or ramipril, combinations of nebivolol and valsartan, or atenolol and amlodipine. Biological samples were processed by protein precipitation techniques or by liquid-liquid extraction. For the determination of fixed dose combinations of felodipine and metoprolol in rat plasma liquid chromatography--electrospray ionization--mass spectrometry (LC-ESI-MS/MS) was applied, using phenacetin as internal standard. HPLC-MS method was applied for the determination of bisoprolol and hydrochlorothiazide in human plasma. For the determination of atenolol and chlorthalidone from human breast milk and human plasma the HPLC method was used. The analytical methods were validated according to the specialized guidelines, and were applied to biological samples, thing that confirms the permanent concern of researchers in this field.

Statistical study on the incidence of allergic diseases treated with desloratadine and levocetirizine at "Atopia" Allergology Medical Center, Iasi, Romania.

UNLABELLED: Allergies and allergic manifestations are a major health problem in our country and around the world. Epidemiological data have reported an increased incidence of allergic diseases up to 10-30% over the past decades. AIM: To evaluate the incidence of the most common allergic diseases treated with desloratadine or levocetirizine, second-generation antihistamines. MATERIAL AND METHODS: For diagnosis and assessment of treatment with the two antihistamines the following tests were performed: allergy skin testing, immunoglobulin E blood levels, evaluation of target organ for allergic reaction (lung function tests, nasal and conjunctival examination, assessment of bronchial inflammation). RESULTS: We conducted a retrospective study that included 365 patients (64% women and 36% men) diagnosed with different types of allergy in the "Atopia" Allergology Medical Center at Iasi during the interval August 2012-August 2013. Patients were aged 2 to 90 years (mean age group 35.98 years; 39.55 years for women, and 29.74 years for men). CONCLUSIONS: The majority of patients were from urban areas (82%). The most common allergic diseases in the study group were: urticaria (21%), allergic rhinoconjunctivitis (14%), allergic bronchitis (14%) and allergic asthma (12%).

Metformin induced lactic acidosis--particularities and course.

Diabetes mellitus is a widespread disease with many serious chronic complications. An improvement in the oral antidiabetic medication in respect to its mechanism of action and toxicology was needed in order to have effective therapies with high compliance and minimum side effects. In this context, metformin is a widely used oral antidiabetic drug, which, through its mechanism of action, has no risk of hypoglycemia. However, a rare but serious side effect of biguanides is lactic acidosis. This paper presents a number of 13 cases of metformin-associated lactic acidosis, which outline the circumstances triggering the adverse event and the clinical therapeutic measures applied in the poisoned patients. The main situations that favor metformin-associated lactic acidosis are renal impairment and tissue hypoxia, and the intervention is adapted to the particular patient condition and symptoms, such as marked hypotension and cardiac arrest. Although there are commonalities in describing the consulted patients, the final prognosis is not dependent on the dose or metformin plasma levels, but rather on the associated pathologies and medication.

[Development and validation of a GC-MS method for determination of nicotine in tobacco]. / Dezvoltarea si validarea unei metode GC-MS pentru determinarea nicotinei din tutun.

UNLABELLED: DETERMINATION FROM TOBA gas chromatographic-mass spectrometric method (GC/MS) for determination of nicotine from tobacco products was developed and validated. MATERIAL AND METHOD: It was used an Agilent Technologies 7890A Chromatograph equipped with a DB 5 MS column (30 m x 0.25 mm, 0.25 microm) and Agilent Technologies 5975C inert MSD detector. The temperature program began from 100 degrees C and increase with 10 degrees C/min to 190 degrees C than with 20 degrees C/min to 280 degrees C, constant for 5 min, with He as carrier gas (1 ml/min) and MS detection. The temperature of the source was 230 degrees C and the temperature of the quadrupole was 150 degrees C. The parameters of validation were studied according to the international requirements. RESULTS: Finally, the method established has following parameters: is linear in the 1.01-201.8 microg/ml range, has the detection limit of 3.6 microg/ml, the quantification limit of 10.8 microg/ml, is precise (RSD < 5%, n = 9) and accurate (mean recovery is 100.28% in 99.08-100.96 microg/ml range). CONCLUSION: The method can be used to determine nicotine from tobacco products, with good results.

[Microbiological evaluation of some commercial brands of Chamomillae floss]. / Controlul microbiologic al unor sorturi comerciale de Chamomillae flos.

UNLABELLED: Different strains of microorganisms contaminate medicinal herb, and theirs, enzymes could modify the normal composition of herbal products. MATERIAL AND METHODS: We evaluated the microbiological quality of 12 samples of Chamomillae floss commercialized in, markets and specific stores. Microbiological quality has been evaluated according European Pharmacopoeia rules. In all samples we determined the total number of germs, total number of fungi and we evaluated the presence of coliform bacilli, respectively Staphylococcus species. RESULTS: For all samples, the total number of germs was under the limits with variation between 320 CFU/g (P 4) and 14000 CFU/g (P 11). The total number of fungi was under the limits; in most of samples, we detected Penicillium sp. and Aspergillus sp. In 4 samples the total number of Escherichia coli strains was over the limits (100 CFU/g). CONCLUSIONS: An important decrease of total number of coliform bacilli was observed after boiling water has been added but the total number of germs was decreased insignificantly, so these extracts are not very safe for patient especially when vegetal products contain a great number of germs.

Serum zinc and copper levels in some dermatological diseases.

UNLABELLED: Zinc (Zn) and copper (Cu) are essential metals for biochemical processes in the body. Many researchers have main interest in these two metals because it was establish that they are involved in immunological and inflammatory reactions. MATERIAL AND METHODS: The study comprised 49 patients of Dermatology Clinic from Iasi with different skin diseases (21 with psoriasis and 28 with varicose ulcer), during January - May 2006. The patients, both sexes, had ages between 19 and 81 years old. We determined serum Zn and Cu levels by atomic absorption spectrophotometry. The results were expressed in mg/L and we calculated Cu/Zn ratio, too; the values were compared with 50 healthy controls. RESULTS: In psoriasis, serum Zn and Cu mean levels (5.61 mg/L, respectively 1.27 mg/L) were higher as compared to controls (significance level p=0.04); the mean Cu/Zn ratio was 0.81 in psoriasis and 0.96 in control group. In varicose ulcer, mean levels were significantly increased (Zn-7.62 mg/L, Cu- 1.38 mg/L) compared to control group (Zn-0.81 mg/L, Cu-0.75 mg/L) and serum normal values; the mean Cu/Zn ratio was 1.00. 18 of all patients with psoriasis and varicose ulcer had higher serum Zn and Cu levels than normal values.

[Lead, nickel and manganese content in edible mushrooms]. / Continutul în plumb, nichel si mangan al ciupercilor comestibile.

The mushrooms accumulate from environmental different kind of pollutants depend by their species, growth phase, and ecological category. For this reason we analysed 55 samples of mushrooms (39 species) with different type of edible proprieties, harvested from Suceava and Iasi County. Samples dried to 105 degree C had been mineralised with nitric acid, by SAA in mineralised had been determined manganese, lead and nickel. From samples 52 (94.54%) contain manganese, 36 contain lead (65.45%) and 28 contain nickel (50.90%). Over 50% of samples contain the greatest quantity of metals in cap comparative with stalk. The highest quantity of metals had been determined in poor edible mushrooms. All samples contain lead over 3 mg/kg with maximum in Chalciporus piperatus (SV 3)--237.40, Clitopilus prunulus-(SV 2)--109.28. The most contaminated samples had been harvested from Rarau Mountainous-Valea Caselor and Bucium-Dobrovat Forest.

[The amount of sulphites in wild mushrooms from Iasi and Suceava districts]. / Cantitatea de sulfiti în ciupercile recoltate din judetele Iasi si Suceava.

As a part of a larger study regarding the contamination of mushrooms from Moldavia by chemical pollutants, we aimed at proposing sulphites determination in samples harvested from different zones from Iasi and Suceava districts, from April to September 2005. We analysed elements (gills, cap, stem) of 68 mushrooms (48 different species). The sulphites were extracted with water, and were analysed spectrophotometrically in the aqueous extract by West-Gaeke method. Results were expressed in microg SO2/g dried product at 105 degrees C. Higher levels of sulphites were found in Clitopilus prunulus (865.36-stem) and Cantharelus cibarius (444.49-cap) for very good edible mushrooms; in Chalciporus piperatus (1016.13-stem) and Pseudohydnum gelatinosum (737.17-all mushroom) for mediocre edible mushrooms; in Panaeolus sphinctrinus (490.11-stem) for toxic ones. In 34 samples (50.74%), the highest level of sulphites was noted mostly in the mushroom stem than in its cap. The mushrooms capacity of sulphite accumulation is very varied, and the results do not allow a correlation between the amount of sulphites found in stem and the one found in cap or gills.

[The amount of nitrites in edible mushrooms harvested from Bistrita Valley]. / Concentratia nitritilor în ciuperci comestibile recoltate de pe Valea Bistritei.

In our study has been determined the amount of nitrites in edible mushrooms which grown in different zones from Bistrita Valley, near to the "Fibrex-nylon" Complex Savinesti. The nitrites has been extracted with water, in the aqueous extract we determined spectrophotometrically nitrites with Griesz Reagent. The results were expressed in mg nitrites/g dried product (105 degrees C). We analysed 41 samples of edible mushrooms (22 samples harvested on october 2001, 19 harvested on september 2002). The nitrites concentrations in mushrooms are between 2.06 and 49.88 (samples harvested on october 2001), between 1.98 and 31.84 (samples harvested on september 2002). The highest values for samples harvested on october 2001 was determined in Laccaria lacata, Collybia butiracea, Hygrophorus chrysodon, Russula nigricans, for the samples harvested on september 2002 the highest values was determined in Boletus granulatus, Macrolepiota procera.

[Delta-aminolevulinic acid measurement in people professionally exposed to lead]. / Determinarea acidului delta-aminolevulinic la persoanele expuse profesional la plumb.

Lead is an enzymatic toxic agent, one of its main effects being the perturbation of the porphyrine biosynthesis. This perturbation can be easily spotted using the rapid method of dosing the delta-aminolevulinic acid in urine (ALA). In this paper there are presented the results of the biotoxicological screening on a segment of population professionally exposed to lead. The exposed group contains 65 persons (50 men and 15 women) with the ages between 20 and 52, employed at different gas stations. Simultaneously, there was determined the concentration of the delta-aminolevulinic acid in urine on a witness group made up of 37 voluntary persons (22 men and 15 women) with the ages between 16 and 58. The delta-aminolevulinic acid in urine was ascertained by spectrophotometry method with Ehrlich reagent. The obtained data were statistically processed by "t student" test. At the exposed group the delta-aminolevulinic acid in urine ranges between 0.14 and 17.0 mg/l, and for each sex between 0.14-17.0 mg/l at men and 4.7-16.5 mg/l at women. The delta-aminolevulinic acid in urine of the witness group ranges between 0.2 and 8.1 mg/l, and for each sex 0.2-5.73 mg/l at men and 1.44-8.1 mg/l at women. The difference between the average value (9.45 +/- 4.47) of the exposed group and the median value of the witness group (3.85 +/- 2.05) is very significant (P < 0.01).

[Malondialdehyde and free thiol groups from smokers' plasma]. / Influenta fumatului asupra malondialdehidei si a gruparilor sulfhidril libere plasmatice.

The nicotine and oxidants from cigarette smoke, could generate oxidative stress in human body. In our study, we determined malondialdehyde and free thiol groups in smokers plasma, the experiment was effectuated to blood donors, smokers (20 persons) and non-smokers (12 persons). The determinations was effectuated with 2-thiobarbituric acid for malondialdehyde and with 5,5'-DTNB for thiol groups. The results was expressed in mmol/L for malondialdehyde and mmol/ml for free thiol groups. Smokers presented higher values for malondialdehyde (1.519 +/- 0.683), than non-smokers (1.362 +/- 0.664). The free thiol groups values was decreased at smokers (0.502 +/- 0.136), than non-smokers (0.517 +/- 0.120). Statistically, insignificant differences (p > 0.05) between smokers and non-smokers, for both parameters, could be determined by the small number of cigarettes smoked (12-15 cigaretts/day), also by the alcohol, because all persons drunk occasionally alcohol.

[Super-oxide dismutase and catalase in smokers]. / Superoxid dismutaza si catalaza la fumatori.

In this work, the results of a study concerning the variation of superoxid dismutase (SOD) and catalase activities to smokers are presented. The study has been performed on volunteers, blood donors, men, between 20-60 years. In the smokers group, 20 donors who smoke over 10 cigarettes/day over 5 years have been included. In the control group, 12 donors who never smoked or stopped to smoke over 4 years have been included. SOD and catalase activities have been determined spectrophotometrically from erythrocytes lysis; the enzymatic activity has been reported to g Hb. The results show a decreasing of SOD activity to smokers reporting to the control group, totally with 17.7% (from 69.6 +/- 18.6 to 57.3 +/- 26.6 U/gHb). Comparing with control group, the catalase has been induced to smokers with 0.04%, from 8.82 +/- 3.32 to 9.18 +/- 8.66 x 10(3) U/gHb. Statistically, the variations are insignificant and we suspect the interferation of alcohol as an important oxidative stress inductor.

Variation of carboxyhemoglobin and of thiocyanates in smokers.

Smoking is one of the most important public health problems of our times. In this paper, we focus on the watching of smoking effect on carboxyhaemoglobin (COHb) and plasma thiocyanate values. The study was accomplished on two groups of blood donors: smokers, 18 men, between 20-51 years old and controls, non-smokers, 10 men, between 22-55 years old. On the blood samples, there have been spectrophotometrically determined: COHb with palladium chloride by microdiffusion method and haemoglobin (Hb) with Drabkin Reagent. The plasmatic thiocyanates were determined spectrophotometrically by Liebig reaction. The data were processed by "t Student" test. The statistical analysis shows that the obtained average values for the COHb from total Hb in smokers (12.51 +/- 10.19) are higher than the average values of the control group (11.45 +/- 10.34). The plasma thiocyanate (mg %) in the smokers' group presents average values of 2.03 +/- 0.58, higher values than those in the control group (1.68 +/- 0.68). From the analysis of the presented results, we notice that the differences between the two groups are statistically non-significantly. These results may be explained by the existence of many factors, which may influence the values of the biotoxicological indicators, among which we mention: passive smoking, the atmospheric pollution in the urban environment, the presence of the chemical noxae at the work place.