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Charcot-Marie-Tooth (CMT) neuropathy is a polygenic disorder of peripheral nerves with no effective cure. Thiamine (vitamin B1) is a neurotropic compound that improves neuropathies. Our pilot study characterizes therapeutic potential of daily oral administration of thiamine (100 mg) in CMT neuropathy and its molecular mechanisms. The patient hand grip strength was determined before and after thiamine administration along with the blood levels of the thiamine coenzyme form (thiamine diphosphate, ThDP), activities of endogenous holo-transketolase (without ThDP in the assay medium) and total transketolase (with ThDP in the assay medium), and transketolase activation by ThDP [1 - (holo-transketolase/total transketolase),%], corresponding to the fraction of ThDP-free apo-transketolase. Single cases of administration of sulbutiamine (200 mg) or benfotiamine (150 mg) reveal their effects on the assayed parameters within those of thiamine. Administration of thiamine or its pharmacological forms increased the hand grip strength in the CMT patients. Comparison of the thiamin status in patients with different forms of CMT disease to that of control subjects without diagnosed pathologies revealed no significant differences in the average levels of ThDP, holo-transketolase, or relative content of holo and apo forms of transketolase. However, the regulation of transketolase by thiamine/ThDP differed in the control and CMT groups: in the assay, ThDP activated transketolase from the control individuals, but not from CMT patients. Thiamine administration paradoxically decreased endogenous holo-transketolase in CMT patients; this effect was not observed in the control group. Correlation analysis revealed sex-specific differences in the relationship between the parameters of thiamine status in both the control subjects and patients with the CMT disease. Thus, our findings link physiological benefits of thiamine administration in CMT patients to changes in their thiamine status, in particular, the blood levels of ThDP and transketolase regulation.

Thiamine deficiency, commonly presenting as dry and wet beriberi, a lesser-known entity in the present era, is increasingly being reported from Kashmir, a north Indian state. The present study aims to present the clinical profile of patients presenting with high-output heart failure (HOHF). Subjects with a primary diagnosis of denovo heart failure and features suggestive of HOHF were recruited; those who responded to intravenous administration of thiamine alone (responders) were adults with no co-morbidities and those who required other medications particularly diuretics (non-responders) were elderly with co-morbidities and underlying heart disease. Responders showed considerably lower mean thiamine pyrophosphate (TPP) levels and higher mean lactate and venous oxygen saturation than non-responders. More importantly, the mean drop in lactate and SVO2 following thiamine therapy was more in responders. In a setting of high risk for thiamine deficiency, features suggestive of HOHF along with elevated lactate and higher venous oxygen saturation, a response to thiamine challenge may serve as surrogate marker of thiamine deficiency., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: We aimed to determine the protective effects of thiamine pyrophosphate on ethanol induced optic neuropathy in an experimental model., Methods: The rats were assigned into 4 groups, with 6 rats in each group as follows: healthy controls (HC group), only ethanol administered group (EtOH group), ethanol + thiamine pyrophosphate (20 mg/kg) administered group (TEt-20 group), and only thiamine pyrophosphate (20 mg/kg) (TPG group) administered group. To the rats in TEt-20 and TPG groups, 20 mg/kg thiamine pyrophosphate was administered via intraperitoneal route. To the rats in HC and EtOH groups, the same volume (0.5 ml) of distilled water as solvent was applied in the same manner. To the rats in TEt-20 and EtOH groups, one hour after application of thiamine pyrophosphate or distilled water, 32% ethanol with a dose of 5 g/kg was administered via oral gavage. This procedure was repeated once a day for 6 weeks. From the blood samples and tissues obtained from the rats, Malondialdehyde (MDA), reduced glutathione (GSH), interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) levels were studied. Histopathological evaluations were performed to the optic nerve tissue., Results: Serum and tissue IL-1β, TNF-α and MDA levels were the highest in EtOH group which were significantly lower in thiamine pyrophosphate administered group (TEt-20 group) (p: 0.001). Serum and tissue reduced GSH levels were the lowest in EtOH group which were also significantly higher in TEt-20 group (p:0.001). In histopathological evaluations, in EtOH group there was obvious destruction and edema with hemorrhage and dilated blood vessels which were not present in any other groups., Conclusions: There was an apparent destruction in ethanol administered group in histopathological analyses with an augmented level of oxidative stress markers and all those alterations were prevented with concomitant thiamine pyrophosphate administration. These protective effects of thiamine pyrophosphate are extremely important in chronic ethanol consumption. Clinical studies are warranted to define the exact role of thiamine pyrophosphate in prevention of ethanol induced optic neuropathy.

Aim: To study the efficacy of the complex therapy, including cocarnit (group B vitamins, triphosadenine and nicotinamide), of diabetic neuropathy., Material and Methods: Forty-one patients with diabetes mellitus type 2 and distal symmetric sensorimotor polyneuropathy were examined. Patients were divided into 2 groups. Patients of the main group (n=26) received complex therapy, including cocarnit, and patients of the comparison group (n=15) received standard treatment., Results and Conclusion: The positive dynamics based on the VAS (р=0.0001), TSS (р=0.0001), NSS (р=0.001), NDS (р=0.0431), SF-36 (р=0.0008), electroneuromyographic results and glycated hemoglobin levels was observed in the main group. In patients of the comparison group, the positive dynamics was instable; the scores of clinical scales did not reach statistical significance. The results suggest the use of cocarnit in the complex treatment of patients with diabetic neuropathy.

Context: Ethambutol-induced retinal oxidative damage in patients with tuberculosis is still not being adequately treated. The protective effect of thiamine pyrophosphate against oxidative damage in some tissues has been reported, but no information on the protective effects of thiamine pyrophosphate against ethambutol-induced oxidative retinal damage has been found in the medical literature., Objective: The objective is to investigate whether thiamine pyrophosphate has a protective effect against oxidative retinal damage in rats induced by ethambutol., Materials and Methods: Experimental animals divided into four groups (n = 10): the healthy group (HG), the ethambutol control group (EMB), thiamine + ethambutol group (Thi-EMB) and thiamine pyrophosphate + ethambutol group (TPP-EMB). The rats in the TPP-EMB and Thi-EMB groups were administered thiamine pyrophosphate and thiamine, respectively, at doses of 20 mg/kg intraperitoneally. Distilled water was administered intraperitoneally to the HG and the EMB groups as a solvent in the same volumes. One hour after drug injection, 30 mg/kg ethambutol was administered via an oral gavage to the TPP-EMB, Thi-EMB and EMB groups. This procedure was repeated once a day for 90 days. At the end of this period, all rats were euthanized under high-dose thiopental sodium anesthesia, and biochemical and histopathological investigations of the retinal tissue were performed., Results: Malondialdehyde (MDA) and DNA damage product 8-hydroxyguanine levels were significantly lower in the retinal tissue of TPP-EMB and HG groups compared to those of the Thi-EMB and EMB groups, and total glutathione (tGSH) was also found to be higher. In addition, severe retinal tissue vascularization, edema and loss of ganglion cells were observed in the Thi-EMB and EMB groups, whereas histopathological findings for the TPP-EMB group were observed to be close to normal., Discussion and Conclusion: These findings suggest that thiamine pyrophosphate protects retinal tissues from ethambutol-induced oxidative damage, and thiamine does not. This positive effect of thiamine pyrophosphate may be useful in the prevention of ocular toxicity that occurs during ethambutol use.

Purpose: To investigate the effects of thiamine pyrophosphate (TPP) against desflurane induced hepatotoxicity., Methods: Thirty experimental animals were divided into groups as healthy (HG), desflurane control (DCG) , TPP and desflurane group (TDG). 20 mg/kg TPP was injected to intraperitoneally TDG. After one hour of TPP administration, desflurane was applied for two hours. After 24 hours, liver tissues of the animals killed with decapitation were removed. The oxidant/antioxidant levels and ALT, AST and LDH activities were measured. The histopathological examinations were performed in the liver tissues for all rats., Results: Notwithstanding the levels of oxidants and liver enzymes were significantly increased (p<0.0001), antioxidant levels were significantly decreased in DCG (p<0.0001). On contrary to the antioxidant parameters were increased (p<0.05) the oxidant parameters and liver enzymes were decreased in TDG (p<0.0001). Whereas multiple prominent, congestion, hemorrhage and dilatation were observed in sinusoids and lymphocyte-rich inflammation results in the centrilobular and portal areas of liver tissue in DCG, these findings were observed less frequently in TDG. CONCLUSİON : Thiamine pyrophosphate prevented liver oxidative damage induced with desflurane and may be useful in prophylaxis of desflurane induced hepatotoxicity.

The aim of this study was to investigate whether thiamine pyrophosphate (TPP) has biochemical and histological preventive effects on oxidative liver damage induced by paracetamol (APAP). Rats were divided into the following groups: healthy control (HG), APAP (AG, 1500 mg/kg, orally), thiamine pyrophosphate (TPPG, 100 mg/kg, intraperitoneally), APAP+NAC (ANAC, 100 mg/kg, intraperitoneally), APAP+TPP (ATPG) and APAP+NAC+TPP (ANTG). Oxidant, antioxidant parameters, liver function tests and histological assessment were performed between groups. Malondialdehyde levels in the AG, HG, TPPG, ANAC, ATPG and ANTG groups were 0.470 ± 0.210, 0.213 ± 0.004, 0.194 ± 0.001, 0.197 ± 0.06, 0.199 ± 0.008 and 0.173 ± 0.010 μmol/g protein, respectively. Total glutathione levels were 7.787 ± 0.395, 14.925 ± 0.932, 13.200 ± 0.984, 13.162 ± 0.486, 13.287 ± 0.787 and 13.500 ± 0.891 μm/g protein, respectively. In the AG group, marked liver damage occurred with the elevation of liver function tests and oxidative stress markers, such as malondialdehyde, myeloperoxidase and nitric oxide (p < 0.05). Biochemical results were congruent with the histological changes of oxidative damage. Compared to the AG group (p < 0.05), TPP significantly reduced oxidant parameter levels in the ATPG group and simultaneously increased the antioxidant parameter levels of catalase and glutathione. The histological changes were improved to almost normal hepatic structure. Moreover, TPP had nearly the same hepatoprotective effect as NAC, and there was statistically no additional benefit with NAC co-treatment. There was no statistically significant difference (p > 0.05) among the ANAC, ANTG and ATPG groups in terms of oxidant/antioxidant levels. TPP proved to be as efficacious as standard therapy and may be beneficial in APAP-induced hepatotoxicity., (© 2015 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

In this paper, the authors conducted research on the application of a new drug for the treatment of diabetic polyneuropathy in patients with diabetes mellitus type 1 and 2. Established an effective influence on the hemodynamic, metabolic, biochemical parameters, improved sensory-motor conduction in nerve fibers. Recommended for widespread use in patients with diabetes mellitus.

In clinical trial included 41 patient with clinic-instrumental dates, which said about myocardium dysfunction and system diseases of connecting fabric and displays of CCI I-III of functional class (FC). Including of complex metabolic drug Cocarnit in standard therapy of systemdiseases of connecting fabric was instrumental in more expressed clinical improvement of patientsclinical dates in 15 days of supervision: a weakness diminished on 66.67%, shortbreathing at the insignificant physical loading--on 23.81%, at the ordinary physical loading--on 47.62%, at the megascopic physical loading--on 19.05%, pain in area of heart--on 42.85%, there are interruptions in-process heart--on 28.57%, oedematousness of shins--on 57.14%, sense of numbness, burning, sensitiveness to cold of extremities--on 57.14%. Quantity of patients with III FC diminished on 5 (23.81%), in a control group--on 2 (10%). It implementation of test with the 6-minute walking more expressed increase of the overcame distance is set for the patients of basicgroup--on 15.46% as compared to a control group--on 7.01%. Cocarnit patients estimatedpositively; side effects with subsequent abolition of drug, were not. Laboratory indexes (AlAT, AsAT, bilirubin, kreatinine, haemoglobin) at the end of trial did not change considerably, that confirmed good bearableness of drug.

In the article the results of clinical researches of efficiency of preparation of Cocarnit are resulted for patients after endoprosthesis of large joints. It is routine that for patients, receiving preparation of Cocarnit after the operation period there was a decline in the amount of complaints of patients on the total somatical state. Preparation of Ccocarnit was positively estimated outside patients, meaningful by-reactions, serving reason of abolition of preparation, was not marked. At the reception preparation of Cocarnit greater part of investigational laboratory indexes (table of contents of glucose, β-lipoproteines, total chondroitisulfates, TBC-productes (malonic dyaldehyde), activity of aspartataminotransferase, alkaline phosphatase and β-glutamyltranspeptidase), the indexes of clinical blood test and leucocytar indexes during a supervision did not have reliable differences from such as the persons of the control group, that confirms good bearab leness of the indicated preparation. Application preparation of Cocarnit for patients in composition the chart of treatment of patients after endoprosthesis of large joints brought maintenance over of cholesterol to the decline, glycoproteins, TBC-products (malonic dyaldehyde), activity of alaninaminotransferase, that specifies on normalizing influence of the indicated preparation in relation to the basic types of exchange of matters.

Objectives: To compare blood thiamine concentrations, echocardiography findings, and plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in infants with clinically diagnosed beriberi and healthy matched controls, and to evaluate changes after thiamine treatment., Study Design: Sixty-two Cambodian infants (20 cases and 42 controls), aged 2-47 weeks, were enrolled in this prospective study. Echocardiography and phlebotomy were performed at baseline and after thiamine treatment., Results: Both cases and controls were thiamine-deficient, with median blood thiamine diphosphate (TDP) concentrations of 47.6 and 55.1 nmol/L, respectively (P = .23). All subjects had normal left ventricular ejection fraction. The median NT-proBNP concentration in cases (340 pg/mL [40.1 pmol/L]) was higher than previously reported normal ranges, but not statistically significantly different from that in controls (175 pg/mL [20.7 pmol/L]) (P = .10), and was not correlated with TDP concentration (P = .13). Two cases with the lowest baseline TDP concentrations (24 and 21 nmol/L) had right ventricular enlargement and elevated NT-proBNP levels that improved dramatically by 48 hours after thiamine administration., Conclusion: Only a minority of thiamine-deficient Cambodian infants demonstrate abnormal echocardiography findings. Thiamine deficiency produces echocardiographic evidence of right ventricular dysfunction, but this evidence is not apparent until deficiency is severe. NT-proBNP concentrations are mildly elevated in sick infants with normal echocardiography findings, indicating possible physiological changes not yet associated with echocardiographic abnormalities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Diabetic foot represents one of the most common complications in patients with a long standing disease. The etiology is neuropathy, infections and ischemia that together contribute to the sequence of tissue necrosis, ulceration and gangrene. Since treatment is very difficult, we must look for several options to solve these problems caused by chronic hyperglycemia. Thiamine pyrophosphate or carboxylase perform multiple metabolic and non-metabolic activities that are considered important in the resolution of diabetic impairments, therefore, this work shows the results when using it in patients with diabetic foot. 29 patients with diabetic foot were treated between January 1998 and July 2012: 19 Wagner type III and 12 Wagner type IV. Management was the administration of antibiotics, partial surgical procedures and thiamine pyrophosphate. The infectious process was controlled, the appearance of granulation tissue and scarring of the lesion in a period of 2 to 6 months depending on the severity of the problem. Given the clinical data and evolution of the patients, we conclude that the administration of thiamine pyrophosphate was able to control metabolic and non-metabolic dysfunctions that lead to complications in diabetic patients, therefore we must consider it a tool in the treatment of diabetic patients in general and for diabetic foot salvage in particular.

This study examines the effect of thiamine (TH) and thiamine pyrophosphate (TPP) on epileptic episode model induced in rats with caffeine. Animals were divided into groups and given TH or TPP at doses of 10, 30 or 50mg/kg intraperitoneally. Subsequently, all animal groups were injected intraperitoneally with caffeine at a dose of 300mg/kg. Time of onset of epileptic episode was recorded, and the latent period was calculated in seconds. At the end of the experiment, tGSH and MDA levels and SOD and MPO enzyme activities in extracted brain tissues were measured. Latent period duration in rats in the control group was 134±3.2s, compared to 144±13.9, 147±14.5 and 169±15.1s, respectively, in the TH10, TH30 and TH50 groups and 184±8.54, 197±9.1, 225±8.37s, respectively, in the TPP10, TPP30 and TPP50 groups. Latent period duration was 236±6.7 in the diazepam group. Oxidant products were significantly lower in the TPP10, TPP30, TPP50 and diazepam groups compared to the control group (P<0.05), while SOD activity and tGSH levels were significantly higher (P<0.05). There was no significant difference between the TH10, TH30, TH50 groups and the control group in terms of oxidant and antioxidant levels (P>0.05). In conclusions, TPP, especially at a dose of 50mg/kg, significantly prolonged the latent period from administration of caffeine to time of episode and prevented oxidative damage., (Copyright © 2013 Elsevier B.V. All rights reserved.)

This study investigated the effects of thiamine pyrophosphate (TPP) at dosages of 10 and 20 mg/kg on oxidative stress induced in rat brain tissue with cisplatin and compared this with thiamine. Cisplatin neurotoxicity represents one of the main restrictions on the drug being given in effective doses. Oxidative stress is considered responsible for cisplatin toxicity. Our results showed that cisplatin increased the levels of oxidant parameters such as lipid peroxidation (thio barbituric acid reactive substance (TBARS)) and myeloperoxidase (MPO) in brain tissue and suppressed the effects of antioxidants such as total glutathione (GSH) and superoxide dismutase (SOD). TPP, especially at a dosage of 20 mg/kg, significantly reduced TBARS and MPO levels that increase with cisplatin administration compared with the thiamine group, while TPP significantly increases GSH and SOD levels. In addition, the level of 8-Gua (guanine), a product of DNA damage, was 1.7 ± 0.12 8-hydroxyl guanine (8-OH Gua)/105 Gua in brain tissue in the control group receiving cisplatin, compared with 0.97 ± 0.03 8-OH Gua/105 Gua in the thiamine pyrophosphate (20 mg/kg) group and 1.55 ± 0.11 8-OH Gua/105 Gua in the thiamine (20 mg/kg) group. These results show that thiamine pyrophosphate significantly prevents oxidative damage induced by cisplatin in brain tissue, while the protective effect of thiamine is insignificant.

Objective: To investigate whether thiamine pyrophosphate can prevent infertility developing in rats undergoing unilateral ovariectomy and with ischemia reperfusion induced in the contralateral ovary. Biochemical examinations of the ovaries were also performed., Study Design: Rats were divided into two main groups of three subgroups each. An ischemia reperfusion model was established in the first main group, while surgical unilateral ovariectomy was performed in the second. Thiamine pyrophosphate and melatonin were administered to the subgroups. No additional procedure was performed in the control groups. The rats were then left in laboratory environments and their fertility levels were determined. Malondialdehyde, total glutathione and DNA damage products were measured in those rats from which ovarian tissue was collected., Results: The results showed that thiamine pyrophosphate prevented ischemia/reperfusion injury-related infertility, but melatonin did not provide adequate prevention. However, reproduction in healthy animals receiving melatonin began earlier compared to those receiving thiamine pyrophosphate. Melatonin suppressed oxidative stress caused by ischemia/reperfusion in ovarian tissue significantly better than did thiamine pyrophosphate., Conclusions: We think that different mechanisms, in addition to antioxidant activity, are involved in the prevention of reperfusion-associated infertility after ischemia., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate the effectiveness of thiamine pyrophosphate against cisplatin-induced ototoxicity in guinea pigs., Materials and Methods: Healthy guinea pigs (n = 18) were randomly divided into three groups. Group 1 (n = 6) received an intraperitoneal injection of saline solution and cisplatin for 7 days, group 2 (n = 6) received an intraperitoneal injection of thiamine pyrophosphate and cisplatin for 7 days, and group 3 (n = 6) received only intraperitoneal injection of saline for 7 days. The animals in all groups were sacrificed under anesthesia, and their cochleas were harvested for morphological and biochemical observations., Results: In group 1, receiving only cisplatin, cochlear glutathione concentrations, superoxide dismutase, and glutathione peroxidase activities significantly decreased (P < 0.05) and malondialdehyde concentrations significantly increased (P < 0.05) compared to the control group. In group 2, receiving thiamine pyrophosphate and cisplatin, the concentrations of enzymes were near those of the control group. Microscopic examination showed that outer hair cells, spiral ganglion cells, and stria vascularis were preserved in group 2., Conclusion: Systemic administration of thiamine pyrophosphate yielded statistically significant protection to the cochlea of guinea pigs from cisplatin toxicity. Further experimental animal studies are essential to determine the appropriate indications of thiamine pyrophosphate before clinical use.

In this study, the biochemical and histopathological effects of thiamine and thiamine pyrophosphate on ischemia-reperfusion induced oxidative damage in rat ovarian tissue were investigated. Animals were divided into four groups of six rat each, ovarian ischemia-reperfusion (IR), 25 mg/kg thiamine + ovarian ischemia-reperfusion (TIR), 25 mg/kg thiamine pyrophosphate + ovarian ischemia-reperfusion (TPIR) and Sham group (SG). The results of the biochemical experiments have shown that the rat ovarian tissue with thiamine treatment, the level of MDA, GSH and the 8-hydroxyguanine are almost the same as the IR group; while in the group with thiamine pyrophosphate treatment, the level of MDA, GSH and the 8-hydroxyguanine are almost the same as the SG. Ovarian tissue of rats in the IR group were congested and dilated vessels, edema, hemorrhage, necrotic and apoptotic cells. In this group, the migration and the adhesion of the polymorphonuclear leucocytes to the endothelium were observed. Both ovaries in TPIR group, there was no difference according to the SG. Histopathology of ovarian tissues in the TIR group was almost the same with the IR group. Our results indicate that thiamine pyrophosphate significantly prevents the ischemia-reperfusion induced oxidative damage in ovarian tissue, whereas thiamine has no effect. In conclusion, we have found that thiamine pyrophosphate prevents oxidative damage due to ischemia-reperfusion injury, whereas thiamine does not have this effect. Furthermore, we have confirmed that the results of our biochemical analyses are in concordance with the histopathological findings.

Objectives: The biochemical effects of thiamine pyrophosphate on ischemia-reperfusion (IR) induced oxidative damage and DNA mutation in rat kidney tissue were investigated, and compared to thiamine., Materials and Methods: Rats were divided into four groups: renal ischemia-reperfusion (RIR); thiamine pyrophosphate + RIR (TPRIR); thiamine + RIR (TRIR); and sham group (SG)., Results: The results of biochemical experiments have shown that malondialdehyde (MDA) levels in rat kidney tissue after TRIR and TPRIR treatment were 7.2 ± 0.5 (P > 0.05) and 3.3 ± 0.3 (P < 0.0001) μmol/g protein, respectively. The MDA levels in the SG rat kidney tissue and in RIR group were 3.6 ± 0.2 (P < 0.0001) and 7.6 ± 0.6 μmol/g protein, respectively. Total glutathione (tGSH) levels in TRIR, TPRIR, SG, and RIR animal groups were 2.2 ± 0.3 (P > 0.05), 5.8 ± 0.4 (P < 0.0001), 6.2 ± 0.2 (P < 0.0001), and 1.7 ± 0.2 nmol/g protein, respectively. In the TRIR, TPRIR, SG, and RIR animal groups; 8-hydroxyguanine (8-OHGua)/Gua levels, which indicate mutagenic DNA, were 1.75 ± 0.12 (P > 0.05), 0.93 ± 0.1 (P < 0.0001), 0.85 ± 0.08 (P < 0.0001), and 1.93 ± 0.24 pmol/L, respectively., Conclusions: It has been shown that thiamine pyrophosphate prevents increase in mutagenic DNA in IR induced oxidative damage, whereas thiamine does not have this effect.

Left ventricular diastolic dysfunction in patients with diabetes is formed in the absence of atherosclerotic changes as a consequence of diabetic cardiac autonomic neuropathy in the early stages of diabetes. Progression of autonomic cardiac neuropathy in cardio-vascular type is associated with the violation of energy supply of cells, protein synthesis, electrolyte exchange, the exchange of trace elements, oxidation reduction processes, oxygen-transport function of blood, so that metabolic therapy is carried out to optimize the processes of formation and energy costs. The drug cocarnit activates processes of aerobic oxidation of glucose, as well as providing regulatory influence on the oxidation of fatty acids. Applying of cocarnit in complex therapy in patients with diabetic cardiac autonomic neuropathy found improvement of left ventricular diastolic function, and positive dynamics in the efferent activity balance of the sympathetic and parasympathetic control of heart rate variability, which provides the regression of clinical symptoms.

Disability after traumatic spinal cord injury (TSCI) results from physical trauma and from "secondary mechanisms of injury" such as low metabolic energy levels, oxidative damage and lipid peroxidation. In order to prove if early metabolic reactivation is a better therapeutic option than antioxidant therapy in the acute phase of TSCI, spinal cord contusions were performed in adult rats using a well-characterized weight drop technique at thoracic 9 level. After TSCI, pyrophosphate of thiamine or non-degradable cocarboxylase (NDC) enzyme was used to maintain energy levels, antioxidants such as superoxide dismutase and catalase (ANT) were used to decrease oxidative damage and methylprednisolone (MP), which has both therapeutic properties, was used as a control. Rats were divided into one sham group and six with TSCI; one of them received no treatment, and the rest were treated with NDC, MP, NDC + MP, NDC + ANT or ANT. The ANT group decreased lactate and creatine phosphokinase levels and increased the amount of preserved tissue (morphometric analysis) as well as functional recovery (Basso, Beattie and Bresnahan or BBB motor scale). In contrast, NDC treatment increased lipid peroxidation, measured through thiobarbituric acid reactive substances (TBARS) levels, as well as spinal cord tissue destruction and functional deficit. Early metabolic reactivation after a TSCI may be deleterious, while natural early metabolic inhibition may not be a "secondary mechanism of injury" but a "secondary neuroprotective response". While increased antioxidant defence after a TSCI may currently be an ideal therapeutic strategy, the usefulness of metabolic reactivation should be tested in the sub-acute or chronic phases of TSCI and new strategies must continue to be tested for the early ones.

Background: We investigated treatment-related changes in oxidative stress indices in intrauterine growth retardation (IUGR) during pregnancy. Four parameters of cell membrane destruction were measured: malondialdehyde, Schiff bases, lipid peroxides, and conjugated dienes., Material/methods: The study population included pregnant women under treatment in the Department of Obstetrics and Gynecology at the Medical University of Łódź in 1997-1999, divided into two groups: (I) - 30 healthy pregnant women, (II) - 31 pregnant women with a clinical and ultrasound diagnosis of IUGR. The course of treatment consisted of ten days of intravenous injections of cocarboxylase, Vitamin C, and solcoseryl as antioxidant factors. The parameters of oxidative stress were measured on the first day of hospitalization, after five days of treatment, and on the 10th day of treatment., Results: The mean value of MDA concentration in Group I was 2.03, vs. 2.39 in Group II. The mean value of conjugated dienes was 2.40 in Group I and 2.41 in Group II. The Schiff bases concentration in Group I was 8.03, as opposed to 8.83 in Group II. The concentration of lipid peroxides was 0.113 in Group I and 0.134 in Group II. We found that all the parameters of oxidative stress were higher in IUGR than in normal pregnancy. At the end of treatment a decrease was observed in all oxidative stress parameters., Conclusions: IUGR is correlated with an increase in membrane damage parameters. Therapy for IUGR decreased the values of all indices of oxidative stress.

A pharmacologic investigation confirmed the possibility of deliberate correction of pharmacological properties of the nonsteroidal anti-inflammatory preparation orthophen in a clinical setting by combining it with those drugs (cimetidin and cocarboxylase) capable of inhibiting elimination of orthophen from the body. In consequence, the level of the drug gets elevated not only in blood plasma but also in the synovial fluid of those joints affected by inflammation, which fact secures high efficiency of the antiinflammatory therapy.

Thirty two cases of acute Wernicke's encephalopathy were observed in a period of 33 months, and prior to the mandatory thiamine enrichment of Australian bread-making flour in 1991. These cases were carefully assessed by multiple tests at specified intervals prior to, and following thiamine administration until discharge from hospital. Structured scoring of neurological signs and symptoms, CT scans, psychometry, nutritional measurements, and liver biopsies were performed. There was variation in the presentation and severity of clinical signs and symptoms and in response to treatment. All patients had alcohol-related liver disease, and the results indicated that fatty liver was important in presentation and in response to treatment with thiamine. Other forms of alcohol related brain damage were present in these patients, most of whom were in the 4th or 5th decade of life and had been drinking beer to excess for more than 20 years.

The authors describe a method for the prediction of the therapeutic effect of energy-stabilizing drugs, that helps rapidly select the optimal individual therapeutic policy. The method is based on measurement of the red cell ATP concentration in the course of in vitro incubation of cells in polyionic medium with the drug, and may be used in various diseases associated with energy metabolism disorders on the cellular level. The authors have used this method for the selection of a thiamine drug to be included in therapy of a diabetic in the period of the disease compensation.

The authors observed disturbances of acid-base equilibrium and levels of carboxyhaemoglobin in 116 cases of CO intoxication. The patients were treated early -- at the place of the accident and during transport to hospital. Oxygen treatment was applied, the acid-base equilibrium disturbances were corrected, especially the metabolic acidosis by using alkaline substances. This management enabled rapid elimination of the poison from the organism and an improvement in the general condition of the patients.

Galactosamine, a selective hepatotoxin, produces in rats histologic alterations, which show the characteristics of severe human viral hepatitis. In the present study the efficacy of two different cofactor regimens (coenzyme A, NAD, alpha lipoic-acid, cocarboxylase) in rats with fulminant galactosamine hepatitis were tested. The results showed an improvement of the short-term survival with a short-term treatment and definitely better survival with a long-term regimen with cofactors.

We examined the effects of cocarboxylase treatment on both the hemodynamic variables and metabolic function during endotoxic shock in dogs. Cocarboxylase inhibited deterioration in metabolic function as reflected by improved pH and base excess as well as maintenance of normal oxygen consumption. Significant improvements in mean arterial pressure and cardiac index were also seen. Cocarboxylase is a major coenzyme of mitochondrial pyruvate dehydrogenase and may exert its beneficial effects via this complex.

A preparation claimed to help patients to break the habit of smoking has recently been introduced. Material released in the mouth from a chewing gum causes an unpleasant taste when tobacco smoke is inhaled. This claim has been investigated in a double-blind trial on sixty subjects, thirty of whom took the active chewing gum and thirty the placebo chewing gum. The subjects each used one piece of chewing gum four times a day over a period of two weeks. This investigation clearly indicates that the active chewing gum is effective as an anti-smoking preparation, when used over a period of two weeks and the effect is still demonstrable one month later, although to a lesser extent.

In patients with active rheumatism the activity of the key enzymes of the pentose cycle -- glucoso-6-phosphatedehydrogenase and transketolase -- increases in the erythrocytes of the peripheral blood parallel with the severity of the inflammatory lesion of the heart. In patients with distrophic changes in the myocardium without concomitant carditis the level of glucoso-6-phosphatedehydrogenase did not change significantly, while the content of transketolase decreased considerably. Antirheumatic therapy helping to reduce the inflammatory reactions in the heart results in a reduction of the level of pentose cycle enzymes. The study of the ratio between glucoso-6-phosphatedehydrogenase and transketolase may prove valuable for an approximate evaluation of the predominance of inflammatory or dystrophic processes in the cardiac muscle.

Cocarboxylase, or thiamine pyrophosphate, is an essential coenzyme in the catabolism of pyruvate. The authors evaluated the effects of a stable cocarboxylase solution in the treatment of an experimentally created acute myocardial infarction in 14 healthy mongrel dogs. The left anterior descending artery was ligated for 60 minutes and data were collected at the following points: A) prior to ligation, B) 15 minutes after ligation, C) 30 minutes after ligation, and D) 60 minutes after ligation. In one group (Group II), cocarboxylase (150 mgm/kg) was given systematically via a central line 15 minutes and 45 minutes after ligation, while in Group I an equal amount of D5W was given. Hemodynamic data include heart rate, systolic and mean arterial pressure, pulmonary wedge pressure, right arterial pressure, and cardiac output. Myocardial O2 consumption was determined by the method of Rooke and Feigl. Electrocardiographic data were also monitored throughout the experiment. In both groups, preligation (point A) hemodynamic data were similar. In Group II, there were beneficial hemodynamic changes versus Group I (expressed as percentage recovery of hemodynamic performance from preligation) at points C and D, with significant (P less than 0.05) decreases in heart rate, increased stroke volume, decreased systemic vascular resistance, and decreased myocardial O2 consumption. EKG criteria also showed improvement in Group II versus Group I. In conclusion, this experiment suggests that cocarboxylase may be beneficial to ischemic canine myocardium by virtue of its favorable systemic hemodynamic effects.

A report is given on a treatment carried out in 1971 in 20 adults alcoholic outpatients by means of intravenously administered carboxylase and vitamin B injections. Under abstinence, a reduction in the addiction, psychic activation and physical recuperation without withdrawal symptoms occurred within a few days. Absolute permanent abstinence, which was aimed at, was observed in seven patients, lasting over a period of three to five years. In another six patients is lasted for several months up to two years. In two alcoholics, an improvement of the condition without a longer lasting abstinence was obtained; five patients could hardly be influenced. A subsequent treatment might probably improve the rate of success obtained with this method. The disturbance of the pyruvate metabolism in chronic alcoholism as a cause of the addiction is discussed.

Male Wistar rats were fed a basal diet, Purina Laboratory Chow, and an oxalate calculi-producing diet (CPD). The CPD was the basal diet containing 3 per cent glycolic acid. Sodium pyruvate, DL-alanine, alpha-keto glutaric acid, thiamine pyrophosphate, and L-glutamic acid were added to the CPD to determine their effectiveness in preventing calculi formation. The effectiveness of methyl glyoxal was determined by adding it to the drinking water. Rats fed CPD for 4 weeks developed calculi in the ureters, bladder, renal tubules, and/or renal pelvis and papilla. Rats in groups fed alanine and/or pyruvate had no calculi in their renal tubules or ureters; additionally, these rats had a significant reduction in incidence and amount of deposits in the renal pelvis and bladder. Rats in groups fed alpha-keto glutaric acid, thiamine pyrophosphate, L-glutamic acid, and methyl glyoxal developed equally or more severe oxalate urolithiasis than those on CPD alone. Results of this study show that either pyruvate or alanine at appropriate levels may be beneficial in preventing oxalate urolith formation.

Personal observations of 5 cases of acute life-endangering ethanol intoxication who were treated in the intensive medical care unit. The authors discuss the mechanism of ethanol-induced changes and the method used in the treatment of this intoxication. They also request that hospital laboratories should provide facilities for performing blood alcohol level determinations in emergencies.