Neuroleptic drugs are essential in the treatment of schizophrenia and many other psychiatric disorders. These drugs do however cause a wide range of side effects which can be very distressing to patients. In particular the acute neurological side effects of parkinsonism, akathisia and dystonia, which are termed extrapyramidal syndromes, can be a limiting factor in the use of these drugs (Weiden et al 1987). Fort Napier Hospital is a large psychiatric referral hospital and the majority of patients admitted require neuroleptic drug treatment. Extrapyramidal side effects are regularly seen amongst these patients. This study was designed to discover the incidence of parkinsonism, akathisia and dystonia amongst patients treated with neuroleptic drugs and what specific factors were responsible for these side effects. Relevant literature on this topic was reviewed and comparable studies done in America, Europe and South Africa are discussed. The study sample consisted of one hundred patients who were examined regularly over a two week period for signs of parkinsonism, akathisia, or dystonia which were rated quantitatively according to specific rating scales. Patient and drug variables were then analysed to assess what factors were responsible for these side effects. The incidence of drug-induced parkinsonism was 29%, akathisia 35% and dystonia 20%. Combinations of these three syndromes were observed resulting in an overall incidence of 47%. High potency drugs such as haloperidol and trifluoperazine were responsible for a large percentage of all the side effects, while of the low potency drugs, thioridazine produced less side effects than chlorpromazine. Oral drugs combined with intramuscular depot drugs resulted in a high incidence of side effects. The phase of treatment was clinically important with dystonia occurring more often within the first three days of treatment, akathisia within ten days and parkinsonism after ten to fourteen days. Other factors that were studied included the patients age, sex and prior history of neuroleptic-induced neurological side effects. Due to the predominantly young patient population in this study, the mean age of those patients who developed parkinsonism was 26,7 years, akathisia 27,5 years and dystonia 25,8 years. These side effects were seen more commonly in males than in females. Of the 27 patients in this study who had a prior history of neurological side effects, 15 (56%) developed similar side effects following re-exposure to neuroleptic drugs. Conclusions derived from this study include the need for clinicians to select the correct type and dose of neuroleptic for individual patients in order to minimize the development of neurological side effects. Accurate, early diagnosis of side effects by regular examination of patients is necessary for effective patient management. Clinicians should be made more aware of the side effects that can develop with the use of neuroleptic drugs and the effect these side effects have on patients. / Thesis (M.Med)-University of Natal, 1993.

Patients with acquired iron overload require chelation therapy using either Desferal or Exjade. Iron in excess may promote free radical formation in the Fenton reaction resulting in severe injuries of heart, liver and endocrine organs. Che1ators that bind ferric iron (Fe+3) in a 1:1 complex (Desferal) sequester it more efficiently than those che1ators that form 2:1 (Exjade) complexes. We initiated synthesis of new chelators derived from the tridentate chelator pyridoxal isonicotinoyl hydrazone (PIH) and its analogs. The aim of the synthesis was to generate chelators that bind iron in a 1:1 complex, which was confirmed for 8LK02, 10LK02, 11LK02 and 15LK03 by spectrophotometry. All novel chelators mobilized iron more efficiently compared to Desferal and Exjade from murine reticulocytes and human myeloid leukemia cells (K562). Additionally, aforementioned four chelators were also more efficient than PIH and were found to be less or equally toxic as Desferal and Exjade.

Diss. (sammanfattning) Uppsala : Uppsala universitet, 2005. / Härtill 4 uppsatser.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

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Agradecemos a compreensão. on 2017-06-30T12:25:51Z (GMT) / Submitted by FELIPE ANDREOTTA CAVAGNA null (cavfelipe@hotmail.com) on 2017-07-03T18:22:57Z No. of bitstreams: 1 Tese completa com ficha catalográfica.pdf: 2297427 bytes, checksum: 8e382c810380d26d332762e12fa2ab64 (MD5) / Approved for entry into archive by Luiz Galeffi (luizgaleffi@gmail.com) on 2017-07-04T16:36:48Z (GMT) No. of bitstreams: 1 cavagna_fa_me_bot.pdf: 2297427 bytes, checksum: 8e382c810380d26d332762e12fa2ab64 (MD5) / Made available in DSpace on 2017-07-04T16:36:48Z (GMT). No. of bitstreams: 1 cavagna_fa_me_bot.pdf: 2297427 bytes, checksum: 8e382c810380d26d332762e12fa2ab64 (MD5) Previous issue date: 2017-04-07 / O câncer de mama é uma doença maligna relativamente comum em mulheres adultas jovens, justificando a preocupação com a potencial toxicidade gonadal relacionada à quimioterapia. É importante considerar o encaminhamento precoce de pacientes jovens com câncer de mama que tenham desejos reprodutivos para especialistas, a fim de discutir sobre a preservação da fertilidade. A criopreservação de embriões ou de oócitos estão entre os principais métodos à disposição, e para conseguir isso, estimulação ovariana controlada (EOC) é o primeiro passo a ser considerado. O presente estudo tem como objetivo apresentar protocolo de estimulação ovariana em para preservação da fertilidade em pacientes com câncer de mama. De novembro de 2014 a dezembro de 2016, 109 pacientes com câncer de mama com menos de 40 anos de idade foram selecionadas para preservar seu potencial reprodutivo. Elas foram divididas de acordo com a fase do ciclo menstrual em que o estímulo ovariano foi iniciado: fase folicular inicial, fase folicular tardia e fase lútea. Para reduzir o tempo necessário da obtenção dos oócitos, este estudo utilizou o princípio do início aleatório, no qual a EOC pode ser iniciada durante qualquer período do ciclo menstrual sem consequências negativas. O letrozol foi utilizado durante toda a estimulação para diminuir as concentrações de estradiol, independentemente da imunohistoquímica tumoral. Na presença de tumores positivos ao estradiol, e indicação de quimioterapia neoadjuvante, o tamoxifeno foi utilizado como uma medida de proteção adicional. Um agonista do GnRH foi utilizado para desencadear a maturação folicular final, diminuindo o risco de síndrome de hiperestimulação ovariana. Foram analisados os seguintes parâmetros: idade das pacientes, dia de início da EOC, número de dias de EOC, dose total de FSH, níveis de estradiol no dia de maturação folicular final, número de oócitos coletados e número de oócitos vitrificados. A idade média dos pacientes foi de 31,27 ± 4,22 anos. A duração média da EOC foi de 10,0 ± 1,39 dias. O número médio de oócitos coletados foi de 11,62 ± 7,96 e o número médio de oócitos vitrificados foi de 9,60 ± 6,87. A concentração média de estradiol no dia do desencadeamento da ovulação foi de 706,30 ± 450,48 pg / mL, e a dose média de FSH administrada foi 2610,00 ± 716,51 UI. Ao comparar os resultados de acordo com a fase do ciclo no qual a EOC foi iniciada, não houve diferenças significativas no número de oócitos colhidos e vitrificados, duração da estimulação ovariana e dos níveis de estradiol no dia do desencadeamento da ovulação. Observou-se uma diminuição estatisticamente significativa da dose total de FSH administrada nos grupos que iniciaram a EOC na fase folicular tardia e na fase lútea, quando comparada com a fase folicular inicial. Esses resultados sugerem que a criopreservação de oócitos ou embriões com um protocolo específico para pacientes com câncer de mama, é eficaz e pode ser oferecida a mulheres jovens submetidas a tratamento citotóxico que têm preocupações relacionadas ao seu futuro reprodutivo. / Breast cancer is a relatively common malignancy in young adult women, justifying the concern about the potential gonadal toxicity related to chemotherapy. It is important to consider early referral of young breast cancer patients with reproductive desires to fertility specialists, in order to discuss the fertility preservation. Embryos or oocytes cryopreservation are among the main methods available, and to achieve that, controlled ovarian stimulation (COS) is the first step to be considered. From November 2014 to December 2016, 109 breast cancers patients under 40 years were enrolled to preserve their reproductive potential. They were divided according to the menstrual cycle status in: initial follicular phase, late follicular phase and luteal phase. In order to reduce the time necessary to obtain the oocytes, this study used the principle of random start, in which the COS can be initiated during any period of the menstrual cycle without negative consequences. Letrozole was used during all stimulation to reduce estradiol concentrations, regardless of tumor immunohistochemistry. In the presence of estradiol positive tumors, and indication of neoadjuvant chemotherapy, tamoxifen was administerd as an additional protective measure. A GnRH agonist was used to trigger ovulation, in order to mitigate the risk of ovarian hyperstimulation syndrome. The following parameters were analyzed: age, day of COS start, number of days required to COS, total FSH dosage, estradiol levels at final follicular maturation day, number of collected oocytes and number of vitrified oocytes. The mean age of patients was 31.27±4.22 years. The average duration of COS was 10.0±1.39 days. The mean number of collected oocytes was 11.62±7.96 and the mean number of vitrified oocytes was 9.60±6.87. The mean estradiol concentration on the day of the trigger was 706.30±450.48 pg/mL, and the mean dose of FSH administered was 2610.00±716.51 IU. When comparing the outcomes according to the phase of the cycle in which COS was commenced, there were no significant differences in the number of oocytes collected and vitrified, ovarian stimulation length and estradiol levels on the day of the trigger. It was observed a statistically decrease of the total FSH dose administered in the groups starting COS in the late follicular phase and in the luteal phase, when compared to the initial follicular phase These results suggest that oocyte or embryos cryopreservation with a specific protocol for breast cancer patients, is effective, safe, and may be offered to young women undergoing cytotoxic treatment who have concerns related to their reproductive future.

CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A HansenÃase à uma doenÃa infecciosa, de evoluÃÃo lenta, transmitida pelo Mycobacterium leprae que acomete nervos e pele. O tratamento especÃfico das pessoas portadoras de hansenÃase foi enfatizado no inÃcio dos anos 80 pela OrganizaÃÃo Mundial de SaÃde (OMS) com o objetivo de curar o indivÃduo da infecÃÃo pelo Mycobacterium leprae e evitar o desenvolvimento de incapacidades. A OMS implementou a poliquimioterapia (PQT) composta pelas drogas dapsona, clofazimina e rifampicina, cuja associaÃÃo evita a resistÃncia medicamentosa do bacilo. A PQT mata o bacilo, evita a evoluÃÃo da doenÃa, e sendo realizada de forma completa e correta, garante a cura da doenÃa. O objetivo geral deste estudo foi avaliar parÃmetros laboratoriais antes e durante a PQT, em uma populaÃÃo de 102 pacientes hansÃnicos, com idade entre 5 e 78 anos, diagnosticados e assistidos no Centro de Dermatologia Dona LibÃnia (CDERM) no perÃodo de Janeiro de 2005 a Janeiro de 2006. Propomos um estudo para avaliaÃÃo da funÃÃo hepÃtica (TGO, TGP, Bilirrubinas Totais e fraÃÃes e Fosfatase Alcalina), renal (UrÃia e Creatinina) e parÃmetros hematolÃgicos (Leucograma, HematÃcrito e Hemoglobina). O estudo foi feito atravÃs da anÃlise laboratorial no soro do paciente para avaliaÃÃo da funÃÃo hepÃtica, renal e sangue total para parÃmetros hematolÃgicos. Destes, 50 (49%) pacientes foram classificados como paucibacilares (PB) e 52 (51%) multibacilares (MB). Teve como metodologia: ficha de investigaÃÃo, revisÃo de prontuÃrio e coleta de sangue antes de iniciar o tratamento e durante o tratamento, com 6 e 12 meses. Dentre os 102 pacientes estudados 48(47%) eram do sexo feminino e 54(53%) do sexo masculino, 12(11,7%) tinham 1 grau incompleto ou eram analfabetos e 6(5,8%) eram de nÃvel superior. Quanto à situaÃÃo financeira, 40(39,2%) nÃo possuÃam renda e 34(33,3%) ganhavam atà um salÃrio mÃnimo. A mÃdia da idade populacional foi de 40,8 anos (DP=19,3), entretanto a incidÃncia de pacientes com idade inferior a 10 anos foi maior no PB. Com relaÃÃo à forma clÃnica, 2(1,9%) eram da forma Indeterminada, 32(31,3%) TuberculÃide, 31(30,3%) Dimorfa, 15(14,7%) Dimorfa/TuberculÃide, 3(2,9%) Dimorfa/Virchowiana e 8(7,8%) da forma Virchowiana. Com relaÃÃo à anÃlise hematolÃgica, a anemia foi a alteraÃÃo mais freqÃente estando presente antes e durante o tratamento, tendo sido mais significativa no grupo MB no sexto mÃs de tratamento. No leucograma, linfocitose e eosinofilia foram as alteraÃÃes mais freqÃentes antes e durante a PQT nos dois grupos PB e MB. Em relaÃÃo aos parÃmetros bioquÃmicos, foram observadas alteraÃÃes nos nÃveis de TGO 6(5,8%) e TGP 5(4,9%) sem significÃncia estatÃstica. Considerando a inexistÃncia de um perfil laboratorial caracterÃstico para a hansenÃase, as alteraÃÃes encontradas em alguns parÃmetros durante a poliquimioterapia, nÃo podem ser atribuÃdas somente aos efeitos adversos deste esquema, e sim tambÃm aos efeitos inerentes à hansenÃase e/ou ao uso da PQT. Para a realizaÃÃo de um tratamento poliquimioterÃpico seguro à necessÃria a realizaÃÃo de exames laboratoriais antes e durante a poliquimioterapia / Leprosy or Hansenâs disease is an infectious disease with slow flow velocity, transmitted by Mycobacterium leprae that attacks nerves and skin. The specific treatment for people who suffer of leprosy was emphasized in the beginning of the 80âs by the World Health Organization (WHO) in order to cure the infection with Mycobacterium leprae and prevent disability. The WHO has implemented a multidrug therapy (MDT) composed of dapsone, rifampicin and clofazimine, an association that prevents bacillus resistance. The MDT kills the bacillus, prevents the aggravation of the disease, and if followed precisely, guarantees the cure of the disease. The objective of this study was to evaluate laboratory parameters, before and during the MDT, in a population of 102 hansenian patients, aged 5 to 78 years, diagnosed and assisted at the Center of Dermatology Dona LibÃnia (CDERM) between January 2005 and January 2006. Evaluation of liver function (GOT, GPT, total bilirubin and fractions and alkaline phosphatase), renal function (urea and creatinine) and haematological parameters (leukogram, hematocrit and hemoglobin) was done through blood serum analysis or patientâs clinical history. A review of patientâs medical records as well as blood tests was done before treatment, after 6 months and after one year. A total of 102 patients participated on the study. Fifty patients (49%) were classified as paucibacillary (PB) and 52 (51%) multibacillary (MB). Social-demographic characteristics showed that 48 (47%) were female and 54 (53%) were male; 12 (11.7%) were either illiterate or have not finished the first grade; 6 (5,8%) were graduating; 40 (39.2%) did not have income and 34 (33.3%) earned no more than the minimum wage. Mean age was 40,8 years (SD = 19,3) and the number of patients younger than 10 years was higher in PB. As to the clinical form, 32 patients (31.3%) presented the tuberculoid form, followed by dimorph (30.3%); dimorph / tuberculoid (14.7%); Virchowian (7.8%); dimorph / Virchowian (2.9%); and undetermined (1.9%). Hematological analysis showed that anemia was the most frequent alteration, being present before and during treatment, and was most significant in the group MB in the sixth month of treatment. The most frequent alterations showed in the leukogram before and during the MDT in both PB and MB groups were lymphocytosis and eosinophilia. Regarding to biochemical parameters, that changes in the levels of GOT (5.8%) and GPT (4.9%) without statistical significance. Considering the lack of a typical laboratory profile for leprosy, the changes found in some parameters during polychemotherapy can not be attributed only to adverse effects of this therapy but to other effects that are inherent to leprosy and the use of MDT. Therefore, a safe polychemotherapy requires the realization of laboratory tests before and during treatment

O objetivo deste estudo é avaliar a eficácia de duas técnicas de acupuntura no controle da náusea e vômito em pacientes portadoras de Carcinoma Invasivo de mama, submetidas à quimioterapia anti-neoplásica. Foram incluídas no estudo 64 pacientes no período de março de 2003 a fevereiro de 2007, do Hospital A.C. Camargo com diagnóstico anatomopatológico de carcinoma invasivo da mama, candidatas à quimioterapia adjuvante com esquemas que incluem doxorrubicina e ciclofosfamida. O estudo foi realizado no primeiro ciclo de quimioterapia. As pacientes foram randomizados em 3 grupos: As pacientes do grupo A, receberam tratamento antiemético convencional com medicamentos. As pacientes do grupo B, receberam o tratamento antiemético convencional e aplicação de acupuntura clássica. As pacientes do grupo C, receberam tratamento convencional e aplicação de acupuntura auricular. As pacientes foram submetidas à auto-avaliação nos primeiros 21 dias após o início da quimioterapia, e conforme os critérios da Common toxicity criteria of the National Cancer Institute (NCI CTC), preencheram a ficha de coleta de dados em relação à náusea e vômito neste período. Quanto à náusea do primeiro ao sétimo dia, encontramos pelo teste de Kruskal-Wallis diferença significativa (p=0.040), sugerindo que a acupuntura diminui a intensidade de náusea deste período, e quanto à duração de dias de pior intensidade também foi significativo (p=0,037) ou seja a acupuntura diminui os dias de pior intensidade.Quando utilizamos o teste de Mann-Whitney encontramos diferença significativa da intensidade de náusea somente entre os grupos A e B (p=0,013), significando que a acupuntura clássica diminui a intensidade de náusea em relação ao grupo controle. Em relação aos dias de pior intensidade de náusea encontramos diferença entre os grupos A e B (p=0,043) e entre grupos B e C (p=0,010) ou seja, a acupuntura clássica diminui os dias de pior intensidade de náusea em relação aos grupos controle e acupuntura auricular. Quanto à gravidade do vômito, do primeiro ao sétimo dia, encontramos pelo teste de Kruskal-Wallis diferença significativa (p=0,036) entre os grupos, sugerindo que a acupuntura diminui a gravidade de vômitos. Pelo teste de Mann-Whitney entre os grupos A e B encontrou-se diferença significativa (p=0,017), ou seja, a acupuntura clássica diminui a gravidade de vômitos comparado ao grupo controle. Quanto ao número de dias de vômito de pior grau entre o primeiro e o sétimo dia encontramos ao aplicar o teste ANOVA diferença significativa entre os grupos (p=0,029), sendo que a acupuntura diminui o número de dias com vômito. O teste t aplicado para os grupos em pares revelou entre grupos A e B (p=0,035), portanto, a acupuntura clássica diminui o número de dias de vômito comparado ao grupo controle. Ao estudarmos a intensidade de náusea entre oitavo e vigésimo primeiro dia encontramos pelo teste de Kruskal-Wallis entre os grupos diferença significativa (p=0,022), sendo que a acupuntura diminui a náusea entre oitavo e vigésimo primeiro dia. Pelo teste de Mann-Whitney entre grupos aos pares encontrou-se diferença significativa entre os grupos A e B (p=0,016), houve diferença entre grupos A e C (p=0,049). Portanto, há diferença significativa entre grupos B e C em relação ao grupo A, ou seja, a acupuntura clássica e auricular diminuem a náusea entre oitavo e vigésimo primeiro dias em relação ao grupo controle. Conclusão: A acupuntura clássica diminui a intensidade e duração de náusea e vômito do primeiro ao sétimo dia pós-quimioterapia. A acupuntura clássica e auricular diminuem a intensidade de náusea do oitavo ao vigésimo primeiro dia pós-quimioterapia. / The purpose of this study is to evaluate the efficacy of two acupuncture techniques in the control of the nausea and vomiting in patients diagnosed of Invasive Breast Carcinoma submitted to chemotherapy. Sixty four patients with pathological diagnosis of Invasive Breast Carcinoma were included in the study during the period of March 2003 to February 2007 at Hospital A.C. Camargo. The patients received adjuvant chemotherapy including doxorubicin and ciclophosphamide. The study was developed during the first chemotherapy cycle. The patients were randomized in 3 groups: Patients of the group A received conventional antiemetic treatment with drug administration. Patients of the group B received conventional antiemetic treatment with drug administration and application of classic acupuncture. Patients of the group C received conventional antiemetic treatment with drug administration and application of auricular acupuncture. During the first 21 days, the patients performed self-reports after receiving the chemotherapy shot, according to the Common toxicity criteria of the National Cancer Institute (NCI CTC). They filled out the data collection instrument related to the nausea and vomiting in this period. As for the nausea from the first to the seventh day, we found statistical significancy (p=0.040) using the Kruskal - Wallis test, suggesting that acupuncture reduces the intensity of nausea in this period. Regarding length of days having worse intensity of nausea in this period, results were statistically significant by ANOVA test (p=0.037) with acupuncture decreasing the number of days of worse intensity. Through the Mann Whitney test, we also found significant difference regarding the intensity of nausea among the groups A and B (p=0.013), showing that classic acupuncture reduces the intensity of nausea when compared to the control group. In relation to the days of worse intensity of nausea we found difference among the groups A and B (p=0.043) and among groups B and C (p=0.010) meaning that classic acupuncture decreases the days of worse intensity of nausea when compared to control group and auricular acupuncture group. As for the severity of the vomit, from the first to the seventh day, we found through Kruskal - Wallis test a significant difference (p=0.036) among the groups, suggesting that acupuncture reduces the severity of the vomits. Using the Mann - Whitney test among the groups A and B a significant difference was found (p=0.017) meaning that classic acupuncture reduces the severity of vomits compared to the control group. As for the number of days of vomit in worse degree between the first and the seventh day, we used the ANOVA test and found significant difference among the groups (p=0.029) with acupuncture reducing the number of days with vomit. The t test applied for the groups in pairs revealed statistical significance among groups A and B (p=0.035) and therefore, classic acupuncture reduces the number of days of vomit compared to the control group. We have analysed the intensity of nausea between eighth and twentieth first day. Through the Kruskal - Wallis test, we found significant difference among the groups (p=0.022) showing that acupuncture also reduces the nausea between eighth and twentieth first day. Analyzing the groups in pairs with the Mann - Whitney test, we found significant difference among the groups A and B (p=0.016) and among groups A and C (p=0.049). Therefore, there is significant difference among groups B and C in relation to the group A. Classic acupuncture and auricular acupuncture reduce the nausea between eighth and twentieth first days when compared to control group. Conclusion: Classic acupuncture reduces the intensity and duration of nausea and vomit from the first to the seventh day after chemotherapy. Classic acupuncture and auricular acupuncture reduce the intensity of nausea from the eighth to the twentieth first day after chemotherapy.

Class of 2016 Abstract / Objectives: To identify common and serious drug-drug interactions involving novel anticoagulant drugs in cancer patients. Subjects: 60 patients who were treated at the Banner University of Arizona Cancer Center between November 1, 2013 and April 1, 2015 with rivaroxaban, dabigatran, or apixaban. Methods: A retrospective chart review was performed for patients who received a NOAC (novel oral anticoagulant) to determine if a medication regimen contained a drug-drug interaction involving the NOAC. Results: When analyzing the DDIs involving rivaroxaban, dabigatran, and apixaban, Micromedex® detected a total of 123 interactions, compared to Lexicomp®, which detected 111 interactions. When using Lexicomp®, there were 59 (32%) instances of no detected interactions, 19 (10%) moderate interactions, 27 (15%) major interactions, and 65 (36%) contraindicated DDIs with rivaroxaban. When using Micromedex®, there were 47 (26%) instances where no interaction was detected, 4 (2%) moderate interactions, and 119 (65%) major interactions, and no interactions were classified as contraindicated with rivaroxaban. Lexicomp® detected 3 (50%) interactions as major, and found no DDIs in 3 (50%) instances for dabigatran, and detected 1 (7%) moderate, 2 (14%) major and 6 (43%) contraindicated interactions for apixaban. Micromedex® detected 3 (50%) interactions as major, and found no DDIs in 3 (50%) instances for dabigatran, and detected 12 (86%) of interactions as major and found no DDIs in 2 (14%) instances for apixaban. Conclusions: There was significant variation in DDI detection between current literature4,5 and the drug information databases, Lexicomp® and Micromedex®, however most interactions detected were major or contraindicated.

Magister Pharmaceuticae - MPharm / Neurodegenerative diseases are multifactorial in nature, and taking the complex nature of these disorders into consideration, multi-target directed ligands may present as better options to treat these disorders than the classic ‘one molecule, one target’ approach. Neurotransmitter amines are catabolized by monoamine oxidase A and B (MAO-A and MAO-B), therefore they have been targeted for the treatment of neuropsychiatric and neurodegenerative diseases. Besides offering a potential antidepressant action in PD, MAO-A inhibitors may also provide a symptomatic benefit by reducing MAO-A-catalysed oxidation of dopamine. The oxidative deamination reaction catalyzed by MAO-B is one of the major catabolic pathways of dopamine in the brain. Inhibition of this enzyme leads to enhanced dopaminergic neurotransmission and are currently used in the symptomatic treatment of PD. Furthermore, MAO-B inhibitors may also exert neuroprotective effects by reducing the concentration of potentially hazardous by-products produced by MAO-B-catalysed dopamine oxidation. Apoptosis or programmed cell death occurs in a number of neurodegenerative disorders and it has been proven that inhibition of the executing enzyme, caspases-3, slows down or even stops apoptosis. Having this in mind we focused on the propargylamine function of selegiline and the fluorophenyl function of safinamide, because of their inherent monoamine oxidase inhibitory activities; and isatin as a non-peptide inhibitor of caspase-3. Therefore we attempted to design and synthesize multifunctional hybrid molecules acting simultaneously to halt the apoptotic neuronal breakdown process and eliminate the signs and symptoms of diseases such as PD. Seven novel compounds were successfully synthesized utilizing multistep processes. The synthesis of 5 chlorosulfonyl isatin was accomplished starting from the commercially available isatin in two steps, which were, sulfonation using tetramethylene sulfone and chlorination with POCl₃. Next 5-chlorosulfonyl isatin was conjugated to the fluorophenylamine derivative with the fluoro-function at either the ortho, meta or para position through a nucleophilic substitution reaction on the chlorosulfonyl position. The resultant compounds were coupled on the N position of the isatin function with propargyl bromide, using a microwave synthesis procedure, in a nucleophilic substitution reaction. The structures and purity were confirmed by nuclear magnetic resonance (NMR) and mass spectrometry (MS). In the biological evaluations recombinant human MAO-A, MAO-B and caspase 3 enzymatic assays were performed to determine the activity of the novel compounds at an enzymatic level. The inhibition percentages for these compounds were calculated and plotted against the logarithm 8 of the inhibitor concentrations to obtain a sigmoidal dose-response curve and consequently the IC50 value. The synthesized compounds showed inhibition of the MAO-A, MAO-B and caspase-3 enzymes at low to high micro molar concentrations. The role of the fluorophenylamine moiety in the synthesized compounds was significant for their multifunctional activity as shown by compounds 3 and 4 having good inhibitory activity towards MAO-A, MAO-B and also excellent inhibitory activity against caspase 3, making those ideal candidates for further lead compound development and multifunctional drug design. The introduction of the propargylamine moiety only increased the MAO-A inhibitory activity; this was shown by compounds 7, 8 and 9 which exhibit good MAO-A selectivity with low MAO-B and caspase-3 inhibitory activities.

Class of 2005 Abstract / Objective: To determine the effect that a pharmacist run diabetes mellitus (DM) care clinic has on glycemic control, as measured by glycosylated hemoglobin (HbA1c) levels. The baseline comparison group is the current standard of care consisting of physician only treated DM patients. Methods: This project is a retrospective cohort analysis of clinical data obtained from patient charts, patients were matched on age. The pharmacist treated group, from a community health center clinic with a collaborative care agreement for the treatment of DM (Group 1), provided comprehensive DM treatment based upon a prearranged treatment protocol with clinic physicians. The physician treated group, is from an outpatient clinic situated at a community hospital (Group 2). The primary outcome was change in HbA1c over at least a 6 month period of time. Patients from both groups were diagnosed with type 2 diabetes mellitus, >18 years of age, and enrolled in an Arizona Health Care Cost Containment System (AHCCCS) Medicaid insurance program. Patients could be treated with oral antidiabetic medication, an insulin product, or a combination of both. Results: A total of 321 patients were included in the study, Group 1 n=161, Group 2 n=160. Ages were similar, mean age=57.7 (SD=12.2) for Group1 and mean age=57.4 (SD=12.3) for Group 2. Gender (male=33.5% and 37.5% respectively) and ethnicity were also similar (p>0.45). The average HbA1c levels at baseline and at the end of treatment were as follows; Group 1 (9.8 and 7.8), and Group 2 (8.8 and 8.9) p<0.001 for post treatment comparison. Implications: This study indicates that physician pharmacist collaborative care improves glycemic control, as shown by significantly lower HbA1c levels than the physician treated group.