Neurofilament heavy subunit in cerebrospinal fluid: a biomarker of amyotrophic lateral sclerosis?

The objectives of this study were to investigate the presence of the three neurofilament subunits, ubiquitin, proteasome and 3-nitrotyrosine, in CSF samples of ALS patients. CSF samples were obtained by lumbar puncture from 10 ALS patients and six controls. All samples were analysed by Western blotting. Results revealed that neurofilament heavy subunit was identified in 70% of ALS cases and we conclude that this subunit may be a promising biomarker for clinical diagnosis of ALS.

Comparação entre o sumatriptano, a trimebutina, o meloxicam e a associação dos três fármacos no tratamento agudo de enxaqueca / Comparison among sumatriptane, trimebutine, meloxicam and the association of those drugs in the acute treatment of migraine

JUSTIFICATIVA E OBJETIVOS: A crise aguda de migrânea geralmente leva a grande incapacidade econômica e social para aqueles que sofrem deste transtorno. A fisiopatologia é complexa e envolve múltiplos mecanismos centrais e periféricos. O tratamento agudo tem como objetivo aliviar a dor e os fenômenos associados como a náusea e fotofobia, sem causar efeitos adversos importantes. Apesar do desenvolvimento de fármacos específicos como os triptanos, para o tratamento agudo, a sua eficácia ainda é baixa. O objetivo deste estudo foi comparar a eficácia e a tolerância da trimebutina, meloxicam, sumatriptano e a associação dos três fármacos no tratamento das crises agudas de migrânea de moderada a forte intensidade.MÉTODO: Após aprovação pelo Comitê de Ética das Instituições foram incluídos neste estudo prospectivo, duplamente encoberto e aleatório, 50 pacientes, sendo 43 mulheres e 7 homens, com idade entre 18 e 65 anos, portadores de migrânea com ou sem aura, que utilizavam medicação profilática, exceto anti-inflamatórios não esteroides (AINES). Foram tratadas quatro crises de migrânea de moderada a forte intensidade de cada paciente, com 200 mg de trimebutina, 50 mg de sumatriptano, 15 mg de meloxicam ou com a associação de 200 mg de trimebutina, 50 mg de sumatriptano e 15 mg de meloxicam. Os pacientes foram aleatorizados em 4 grupos de acordo com a ordem de chegada, de modo que o primeiro paciente incluído recebeu trimebutina para a primeira crise, sumatriptano para a segunda crise, meloxicam para a terceira crise e a associação entre os 3 fármacos para a quarta crise. O segundo paciente incluído recebeu sumatriptano para a primeira crise, meloxicam para a segunda superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.crise, a associação para a terceira crise e a trimebutina para a quarta crise, e assim sucessivamente. A intensidade da crise de migrânea foi avaliada a partir da ingestão da cápsula com escala categorizada verbal na qual: 0 - sem dor, 1 - cefaleia leve, 2 - cefaleia moderada e 3 - cefaleia intensa. Cada paciente foi orientado para preencher o relatório de crise para cada crise tratada, na qual anotava a intensidade da cefaleia, a presença de náusea, fotofobia e dos efeitos adversos, e o uso da medicação de resgate, 100 mg de indometacina por via retal. RESULTADOS: Completaram o estudo 42 pacientes. Em uma hora 9,5% dos pacientes que utilizaram a associação dos fármacos estavam livres da dor, comparados com 14,2% com a trimebutina e sumatriptano e 2,4% com o meloxicam (p = 0,479). Em duas horas 21,4% dos pacientes que usaram a associação estavam livres da dor, comparados com 11,9% com a trimebutina, 26,1% com sumatriptano e 23,8% com o meloxicam (p = 0,555). Tanto a associação trimebutina, sumatriptano e meloxicam como os fármacos trimebutina, sumatriptano e meloxicam isolados foram efetivos para controlar a náusea e fotofobia após 1 e 2h para náusea (p = 0,157 e 0,587) e fotofobia (p = 0,671 e 0,929, embora sem diferença estatisticamente significativa entre eles. Dez pacientes em uso da associação dos fármacos, 6 em uso da trimebutina, 5 em uso do sumatriptano e 5 em uso do meloxicam relataram efeitos colaterais. CONCLUSÃO: Este estudo demonstrou que a associação sumatriptano, meloxicam e trimebutina não foi superior a cada um desses fármacos isolados para controlar a dor, as náuseas e a fotofobia nas crises agudas de migrânea de moderada a forte intensidade. Além disso, a combinação dos fármacos apresentou maior incidência de efeitos adversos.

BACKGROUND AND OBJECTIVES: Acute migraine crisis often leads to major economic and social disability for those suffering from such syndrome. Pathophysiology is complex involving several central and peripheral mechanisms. The acute treatment aims at evaluating pain and associated phenomena, such as nausea and photophobia, without causing major adverse effects. Notwithstanding the development of specific drugs for the acute treatment, such as triptanes, their efficacy is still low. This study aimed at comparing efficacy and tolerance of trimebutine, meloxicam, sumatriptane and the association of such drugs to treat moderate to severe acute migraine crises.METHOD: After the Institutions? Ethics Committee approval, participated in this prospective, double-blind and randomized study 50 patients, being 43 females and 7 males, aged between 18 and 65 years, with migraine with or without aura, under prophylactic medication, except non-steroid anti-inflammatory drugs (NSAIDS). Patients were treated for 4 moderate to severe migraine crises with 200 mg trimebutine, 50 mg sumatriptane, 15 mg meloxicam, or with the association of 200 mg trimebutine, 50 mg sumatriptane and 15 mg meloxicam. Patients were randomized in 4 groups according to their arrival, so that the first patient included received trimebutine for the first crisis, sumatriptane for the second crisis, meloxicam for the third crisis and the association of the three drugs for the fourth crisis. The second patient included received sumatriptane for the first crisis, meloxicam for the second crisis, the association for the third crisis and trimebutine for the fourth crisis, and so on and so forth. Migraine crisis intensity was evaluated as from the ingestion of the first tablet with verbal categorized scale where: 0 = no pain, 1 = mild headache, 2 = moderate headache, 3 = severe headache. All patients were oriented to fill a crisis report for each treated crisis, where they would record headache intensity, presence of nausea, photophobia and adverse effects and the use of rescue medication, 100 mg of rectal indometacin.RESULTS: Forty-two patients completed the study. In one hour 9.5% of patients using the association of drugs were free of pain, as compared to 14.2% with trimebutine and sumatriptane and 2.4% with meloxicam (p = 0.479). In two hours 21.4% of patients using the association were free of pain, as compared to 11.9% with trimebutine, 26.1% with sumatriptane and 23.6% with meloxicam (p = 0.555). Both the association of trimebutine, sumatriptane and meloxicam and trimebutine, sumatriptane and meloxicam alone were effective to control nausea and photophobia after 1 and 2 h for nausea (p = 0.157 and 0.587) and photophobia (p = 0.671 and 0.929) although without statistically significant difference among them. Ten patients under the association of drugs, 6 under trimebutine, 5 under sumatriptane and 5 under meloxicam have reported side effects. CONCLUSION: This study has shown that the association of sumatriptane, meloxicam and trimebutine was not better than each of those drugs alone to control pain, nausea and photophobia during moderate to severe migraine crises. In addition, the combination of drugs has shown a higher incidence of adverse effects.

Treatment of acute, non-traumatic pain using a combination of diclofenac-cholestyramine, uridine triphosphate, cytidine monophosphate, and hydroxycobalamin.

This randomized, controlled, double-blind clinical study in parallel groups evaluated the safety and efficacy of an oral combination diclofenac-cholestyramine, nucleotides (uridine and cytidine) and vitamin B12 versus the oral combination of nucleotides and vitamin B12 in the treatment of acute, non-traumatic pain. Subjects received twice-daily, 10-day oral administration of diclofenac-cholestyramine + uridine + cytidine + vitamin B12 (Group DN, n=40) or uridine + cytidine + vitamin B12 (Group NB, n=41). The primary study endpoint was the number of subjects with VAS reduction of >30mm after 10 days of treatment. Secondary endpoints included the number of patients with improvement >5 points in the Patient Functionality Questionnaire after 10 days of treatment, and the number of subjects presenting adverse events. Treatment with the combination of diclofenac-cholestyramine, nucleotides and Vitamin B12 resulted in a higher number of subjects with VAS score reductions >30mm after 10 days of treatment (87.5% subjects) than in the control group administered nucleotides and Vitamin B12 (51.23% of subjects), (p>0.0006). A significantly higher number of subjects in the DN group (80%) had a score reduction of >5 points in the Patient Functionality Questionnaire at after 10 days of treatment compared to Group NB (29.3%), (p<0.001). The number of subjects presenting AEs did not vary significantly between treatment groups (p=0.587). The combination of diclofenac-cholestyramine with uridine, cytidine and vitamin B12 was well-tolerated over a 10-day treatment period. The combination reduced pain and improved functionality among subjects presenting acute, non-traumatic pain in the lower back, hips, and neck.

Treatment of inflammatory neuropathy with dexamethasone plus B-vitamins: a clinical evaluation / Tratamento de neuropatia inflamatória com a associação de dexametasona e vitaminas B: uma avaliação clínica

We evaluated the use of a combination of vitamins B1, B6, and B12 with dexamethasone in the treatment of the signs and symptoms of inflammatory neuropathy of the upper and lower limbs, in an open-label clinical trial. Patients were submitted to a 9-day treatment period with three doses of study medication at three day intervals, and a series of clinical and laboratory assessments, prior to the first dose of study medication and at each of the following three visits to the study center. Efficacy evaluations at each study visit included a 100mm VAS pain scale and global and satisfaction surveys completed by the patient and the investigating physician. Safety evaluations included a comparison of changes in laboratory evaluations at each visit and the incidence, severity, duration, and outcome of adverse events. A total of sixty-one patients were enrolled in the trial. A clinically significant improvement in all of the efficacy measures was observed from the pre-treatment to end-of-study evaluations. No clinically significant alterations in clinical assessments were observed during the treatment period. Based on the results of this clinical study, we conclude that the combination of dexamethasone with the B-vitamins is safe and effective in the treatment of the signs and symptoms of inflammatory neuropathy.

Efficacy and tolerability of a combination of uridine, cytidine, and vitamin B12 in anemia. A double-blind, comparative study versus nucleotide monotherapy

Background: Deficiency in vitamin B12 is commonly associated with pernicious anemia, presenting a number of clinical symptoms resulting from neurological alterations due to modifications in myelin formation. Treatment consists of oral or parenteral vitamin B12 supplementation. Vitamin B12 has also been shown to have analgesic action whether administered alone or in combination with other therapeutic agents. Oral or parenteral pyrimidine ribonucleotide supplementation may be advantageous in the treatment of peripheral neuropathies. Objectives: To evaluate and compare the efficacy and tolerability of an orally administered combination of vitamin B12, uridine and cytidine, versus administration of the nucleotides alone in the treatment of the signs and symptoms of anemia. Study design: Study goal was normalization of MCV and MCH and serum vitamin B12 as well as improvement in pain and paresthesia among patients presenting these symptoms at Pretreatment. The study was designed as a double-blind, randomized trial in two arms: Group A patients were treated with the vitamin + nucleotide combination Group B patients received nucleotides alone. Treatment lasted 60 days, with two interim visits at 20 and 40 days of treatment and a final evaluation after 60 days of treatment. Setting: Patients were attended in an ambulatory setting of a UNIFESO university hospital. Patients: Eligible patients were between 18-65 years of age, with clinical and laboratory presentation of anemia with or without underlying autoimmune disease, caused by vitamin B12 deficiency. Female patients were not pregnant and were required to use birth control for the duration of the treatment period. Eighty patients were randomized, with 40 patients in each treatment group. Treatment consisted of 3 daily oral doses of: 1.0 mg hydroxocobalamin acetate, 2.5 mg cytidine 5'-{sodium P'(2-(trimethylammonio)-ethyl) hydrogen diphosphate}, and 1.5 mg uridine 5'-trisodium triphosphate for Group A patients, while patients in Group B received 2.5 mg cytidine 5'-{sodium P'(2-(trimethylammonio)-ethyl) hydrogen diphosphate}, and 1.5 mg uridine 5'-trisodium triphosphate in identical capsule forms. Main outcome measure: Primary outcome measures defined in the protocol included improvements in MCV, MCH and vitamin B12 reaching laboratory reference range, 3-point improvements in Global, Pain, and Paresthesia evaluations and a 20% reduction in VAS scores. Results: Normalization of laboratory evaluations occurred only in Group A. Three-point improvement in Global evaluation by the physician was observed only in Group A, while both groups showed improvement in Global evaluation by the patient. Patient's assessment of pain improved only in Group A, although VAS score decrease was noted in both groups both groups also had improvement in paresthesia evaluations. Vital signs did not change, while weight gain was observed in both groups. Adverse events seen in both groups included nausea, diarrhea, headache and abdominal cramps. Alterations in laboratory evaluations were reported in both groups, but could be directly attributed to anemia. Conclusion: The combination of vitamin B12, uridine and cytidine was found to be safe and effective in the treatment of the signs and symptoms of anemia in the population studied. The pain reduction observed in both groups may be attributed to activity of the nucleotides.

Evaluation of the safety and efficacy of an injectable B-vitamin combination in acute neuralgias

A clinical trial evaluating the safety and efficacy of the use of an intramuscular combination of vitamins B1, B6, and B12 in the treatment of the signs and symptoms of trigeminal and plantar neuralgia was performed. Patients were submitted to a 9-day, open-label treatment period with three administrations of the study medication, and underwent a series of clinical and laboratory evaluations prior to the first treatment dose and at each of the three following visits to the study center. The incidence of adverse events and the use of concomitant medications was monitored at each study visit, when efficacy evaluations were also performed, including a 100mm VAS pain assessment and global and satisfaction surveys completed by the patients and investigating physician. Additionally, at the end of the treatment period, the patients were evaluated on their willingness to continue treatment with the study medication.

Lysine clonixinate vs naproxen sodium for the acute treatment of migraine: a double-blind, randomized, crossover study.

BACKGROUND AND OBJECTIVES: The process of inflammation is crucial in migraine, and several nonsteroidal anti-inflammatory drugs (NSAIDs) are effective in the treatment of migraine attacks. Despite their efficacy, the routine use of NSAIDs is limited by side effects as well as incomplete efficacy in some patients. Among the available options, lysine clonixinate (LC) and naproxen sodium (NS) have proved effective in migraine. The aim of this study was to compare the efficacy and tolerability of oral formulations of LC and NS in the treatment of moderate or severe migraine attacks, with a double-blind, crossover design. METHODS: Seventy subjects (62 women, 8 men) between ages 18 and 71 years (mean age, 41) with migraine according to the criteria of the International Headache Society were prospectively enrolled. The patients were randomized into 2 groups and each participant treated 2 migraine attacks. Group 1 treated the first attack with LC and the second attack with NS. Group 2 treated 2 attacks in a counterbalanced order. Doses were 250 mg of LC or 550 mg of NS, which were encapsulated for equal appearance. Headache intensity, nausea, photophobia, and side effects were evaluated at baseline, 1 hour, and 2 hours after drug administration. Rescue drugs were allowed after 2 hours for those who didn't respond, and this was also compared between groups. RESULTS: Sixty patients (54 women, 6 men) completed the study. At 1 hour, 13.6% patients who used LC were pain-free compared with 11.9% who used NS (P = .78). At 2 hours, 35.6% patients who took LC and 32.2% who took NS were pain-free (P = .69). At baseline, 52.5% of the patients randomized to group 1 reported nausea, compared with 33.9% in group 2, and both drugs eliminated nausea: At both 1 hour and 2 hours, nausea diminished significantly for those taking LC, but only after 2 hours for those who took NS (P < .0001). Both drugs eliminated photophobia at 1 hour and 2 hours; however, LC was superior to NS in reducing photophobia at 2 hours (P = .027). Ten patients who took LC and 8 who took NS required rescue drugs after 2 hours. Twelve patients who used LC and 16 who took NS reported side effects. COMMENTS: Although this study did not include a placebo arm, which impairs any definitive efficacy claims, we found LC and NS to be similarly effective and well tolerated in patients presenting moderate or severe attacks of migraine.