A hiperplasia adrenal congênita (HAC) é um grupo de doenças hereditárias causadas por uma deficiência em uma das enzimas necessárias para a síntese de cortisol no cortex adrenal. Mais de 95% de todos os casos de HAC são devidos a 21-Hidroxilase (21-OHD). Existem 3 formas principais, duas com manifestações clínicas no período neonatal, a forma mais grave perdedora de sal (HAC-PS) e a forma virilizante simples (HAC-VS). Além da perda salina, o excesso de andrógenos leva à virilização de recém nascidas femininas. As formas neonatais são chamadas de clássicas, atividade enzimática da 21-OH bastante reduzida, de < 2% na HAC-PS e de 2-10% na HAC-VS. A forma parcial de início tardio é chamada de HAC não clássica (HAC-NC) e a principal manifestação na infância é a adrenarca precoce. Nesta forma a atividade da 21-OH é de 20-60%. Os programas de triagem para HAC visam, principalmente, ao diagnóstico precoce da forma clássica perdedora de sal, mais grave e potencialmente letal. No Brasil, a triagem pública é realizada no Estado de Goiás desde 1997 e em Santa Catarina desde 2001. No Rio Grande do Sul (RS) foi implantada em maio de 2014 na fase IV do Programa Nacional de Triagem Neonatal. A inclusão da HAC trouxe consigo muitos desafios e a exigência de um fluxo de triagem e diagnóstico bem estruturados. O diagnóstico precoce é crucial para prevenir o óbito de lactentes por insuficiência adrenal. Dosa-se, em papelfiltro, a 17OH progesterona (17-OHP). Elevações podem ocorrer em recém-nascidos sem HAC (falso-positivos), devido a situações de estresse perinatal e por prematuridade. Após avaliação dos dados do primeiro ano de triagem para HAC neste estudo, a mediana da idade da coleta nos casos diagnosticados foi de 8 dias (4.25-15.75). Dos 8 casos diagnosticados de maio de 2014 a abril de 2015, 6 casos com forma perdedora de sal (incluindo 1 caso de óbito por coleta tardia do TP aos 38 dias de vida). A incidência encontrada em nosso meio no primeiro ano foi de 1:13.551 casos. Com a estratégia do uso de pontos de corte estratificados pelo peso de nascimento18, o índice total de resultados positivos em nosso meio foi de 0,5% da amostra avaliada (“n” total de 514 bebês), sendo mais frequente em recém nascidos com menos de 2000g de peso ao nascer. Além da confirmação clínica e laboratorial, o genótipo é importante, além de confirmar, para estabelecer gravidade da doença e também para ratificar o diagnostico dos falsos positivos na ausência de uma mutação do gene CYP21A2. Um dos casos confirmados de HAC-PS foi associado a múltiplas malformações e craniossinostose severa, suscitando a hipótese de um a associação com defeito de FGFR2. A correlação genótipo- fenótipo na avaliação dos casos em dois anos da triagem alcançou um alto nível de concordância de 87%. Diagnosticada, portanto, de forma assertiva a HAC forma clássica, instituise a terapia glicocorticóide para as formas virilizante simples e acrescenta-se mineralocorticóide para as formas perdedoras de sal. A triagem neonatal é um importante programa de saúde populacional e visa ao diagnóstico precoce de uma patologia com potencial risco à vida pela perda de sal, além de permitir adequada atribuição de sexo nas meninas com virilização genital e à saúde da criança. Estabelecer os fluxos adequados de triagem e manejo, além de ampliar o conhecimento sobre a HAC, com o reconhecimento dos desfechos e tratamentos adequados é essencial para minimizar as possíveis complicações nesta população de maior vulnerabilidade. / Congenital adrenal hyperplasia (CAH) is a group of inherited diseases caused by a deficiency in one of the enzymes required for the cortisol synthesis by the adrenal cortex. More than 95% of all CAH cases are due to 21-hydroxylase (21-OHD). There are 3 forms, two with neonatal clinical manifestation: salt-wasting CAH (SW-CAH\) and the simple virilizing form (HAC-VS). In addition to salt loss, androgens excess lead to the virilization of female newborn. Neonatal forms are defined as classical CAH. The 21-OHD enzymatic activity in SWCAH is less than <2% and in the SV-CAH 2-10%. A late-onset form, with partial enzymatic defect (20-60%) is called non-classical HAC (NC-CAH) and the main manifestation in childhood is early adrenarche. In Brazil, public health screening has been conducted in the State of Goiás since 1997 and in te Sate of Santa Catarina since 2001. In Rio Grande do Sul (RS) it was implemented in May 2014, in phase IV of the National Neonatal Screening Program. The inclusion of CAH in the local screening program brought many challenges and the need of a well structured screening and diagnosis flowchart. Early diagnosis is crucial to prevent infant death due to adrenal insufficiency. Around de world, the screening programs for CAH main purpose is the early diagnosis of the more severe classical forms, especially SW-CAH. The cortisol precursor 17OH progesterone (17-OHP) is the main disease marker and is measured on filter paper. Elevations may occur in infants without CAH (false positive) due to perinatal stress and prematurity. Of newborns screened in the first year, median age of collection in diagnosed cases was 8 days (4.25-15.75) and 8 patients were diagnosed with CAH (four males, four females). The incidence of CAH in the state was 1:13,551. Six cases were identified as classic salt-was-ting CAH and two were cases of virilizing CAH. The overall rate of positive results was 0.5% (n = 514 infants). The number of false positive results was higher among newborns with birth weight < 2,000 g. In addition to clinical and laboratory confirmation, the genotype is important to confirme 21-OH deficiency, to establish disease severity and also in the absence of a mutation of the CYP21A2 gene to more precise exclude the diagnosis of suspected false positives. One of the confirmed cases of SW-CAH was associated with multiple malformations and severe craniosynostosis, raising the hypothesis of an association with FGFR2 mutation. A high genotype- phenotype correlation of 87% was found in the cases after two years of screening. Once the classic CAH is diagnosed, glucocorticoid therapy is instituted and mineralocorticoid is added for SW-CAH. CAH neonatal screening is an important population health program and aims to the early diagnosis of a pathology with a potential risk due to salt loss crisis. The early detection of cases also allows to adequate sex assignment in girls with genital virilization. Establishing adequate screening flows, proper diagnosis and management, in addition to increase knowledge about the disease, with the appropriate recognition of outcomes and treatments is essential to minimize complications in this population of greater vulnerability.

A hiperplasia adrenal congênita (HAC) é um grupo de doenças hereditárias causadas por uma deficiência em uma das enzimas necessárias para a síntese de cortisol no cortex adrenal. Mais de 95% de todos os casos de HAC são devidos a 21-Hidroxilase (21-OHD). Existem 3 formas principais, duas com manifestações clínicas no período neonatal, a forma mais grave perdedora de sal (HAC-PS) e a forma virilizante simples (HAC-VS). Além da perda salina, o excesso de andrógenos leva à virilização de recém nascidas femininas. As formas neonatais são chamadas de clássicas, atividade enzimática da 21-OH bastante reduzida, de < 2% na HAC-PS e de 2-10% na HAC-VS. A forma parcial de início tardio é chamada de HAC não clássica (HAC-NC) e a principal manifestação na infância é a adrenarca precoce. Nesta forma a atividade da 21-OH é de 20-60%. Os programas de triagem para HAC visam, principalmente, ao diagnóstico precoce da forma clássica perdedora de sal, mais grave e potencialmente letal. No Brasil, a triagem pública é realizada no Estado de Goiás desde 1997 e em Santa Catarina desde 2001. No Rio Grande do Sul (RS) foi implantada em maio de 2014 na fase IV do Programa Nacional de Triagem Neonatal. A inclusão da HAC trouxe consigo muitos desafios e a exigência de um fluxo de triagem e diagnóstico bem estruturados. O diagnóstico precoce é crucial para prevenir o óbito de lactentes por insuficiência adrenal. Dosa-se, em papelfiltro, a 17OH progesterona (17-OHP). Elevações podem ocorrer em recém-nascidos sem HAC (falso-positivos), devido a situações de estresse perinatal e por prematuridade. Após avaliação dos dados do primeiro ano de triagem para HAC neste estudo, a mediana da idade da coleta nos casos diagnosticados foi de 8 dias (4.25-15.75). Dos 8 casos diagnosticados de maio de 2014 a abril de 2015, 6 casos com forma perdedora de sal (incluindo 1 caso de óbito por coleta tardia do TP aos 38 dias de vida). A incidência encontrada em nosso meio no primeiro ano foi de 1:13.551 casos. Com a estratégia do uso de pontos de corte estratificados pelo peso de nascimento18, o índice total de resultados positivos em nosso meio foi de 0,5% da amostra avaliada (“n” total de 514 bebês), sendo mais frequente em recém nascidos com menos de 2000g de peso ao nascer. Além da confirmação clínica e laboratorial, o genótipo é importante, além de confirmar, para estabelecer gravidade da doença e também para ratificar o diagnostico dos falsos positivos na ausência de uma mutação do gene CYP21A2. Um dos casos confirmados de HAC-PS foi associado a múltiplas malformações e craniossinostose severa, suscitando a hipótese de um a associação com defeito de FGFR2. A correlação genótipo- fenótipo na avaliação dos casos em dois anos da triagem alcançou um alto nível de concordância de 87%. Diagnosticada, portanto, de forma assertiva a HAC forma clássica, instituise a terapia glicocorticóide para as formas virilizante simples e acrescenta-se mineralocorticóide para as formas perdedoras de sal. A triagem neonatal é um importante programa de saúde populacional e visa ao diagnóstico precoce de uma patologia com potencial risco à vida pela perda de sal, além de permitir adequada atribuição de sexo nas meninas com virilização genital e à saúde da criança. Estabelecer os fluxos adequados de triagem e manejo, além de ampliar o conhecimento sobre a HAC, com o reconhecimento dos desfechos e tratamentos adequados é essencial para minimizar as possíveis complicações nesta população de maior vulnerabilidade. / Congenital adrenal hyperplasia (CAH) is a group of inherited diseases caused by a deficiency in one of the enzymes required for the cortisol synthesis by the adrenal cortex. More than 95% of all CAH cases are due to 21-hydroxylase (21-OHD). There are 3 forms, two with neonatal clinical manifestation: salt-wasting CAH (SW-CAH\) and the simple virilizing form (HAC-VS). In addition to salt loss, androgens excess lead to the virilization of female newborn. Neonatal forms are defined as classical CAH. The 21-OHD enzymatic activity in SWCAH is less than <2% and in the SV-CAH 2-10%. A late-onset form, with partial enzymatic defect (20-60%) is called non-classical HAC (NC-CAH) and the main manifestation in childhood is early adrenarche. In Brazil, public health screening has been conducted in the State of Goiás since 1997 and in te Sate of Santa Catarina since 2001. In Rio Grande do Sul (RS) it was implemented in May 2014, in phase IV of the National Neonatal Screening Program. The inclusion of CAH in the local screening program brought many challenges and the need of a well structured screening and diagnosis flowchart. Early diagnosis is crucial to prevent infant death due to adrenal insufficiency. Around de world, the screening programs for CAH main purpose is the early diagnosis of the more severe classical forms, especially SW-CAH. The cortisol precursor 17OH progesterone (17-OHP) is the main disease marker and is measured on filter paper. Elevations may occur in infants without CAH (false positive) due to perinatal stress and prematurity. Of newborns screened in the first year, median age of collection in diagnosed cases was 8 days (4.25-15.75) and 8 patients were diagnosed with CAH (four males, four females). The incidence of CAH in the state was 1:13,551. Six cases were identified as classic salt-was-ting CAH and two were cases of virilizing CAH. The overall rate of positive results was 0.5% (n = 514 infants). The number of false positive results was higher among newborns with birth weight < 2,000 g. In addition to clinical and laboratory confirmation, the genotype is important to confirme 21-OH deficiency, to establish disease severity and also in the absence of a mutation of the CYP21A2 gene to more precise exclude the diagnosis of suspected false positives. One of the confirmed cases of SW-CAH was associated with multiple malformations and severe craniosynostosis, raising the hypothesis of an association with FGFR2 mutation. A high genotype- phenotype correlation of 87% was found in the cases after two years of screening. Once the classic CAH is diagnosed, glucocorticoid therapy is instituted and mineralocorticoid is added for SW-CAH. CAH neonatal screening is an important population health program and aims to the early diagnosis of a pathology with a potential risk due to salt loss crisis. The early detection of cases also allows to adequate sex assignment in girls with genital virilization. Establishing adequate screening flows, proper diagnosis and management, in addition to increase knowledge about the disease, with the appropriate recognition of outcomes and treatments is essential to minimize complications in this population of greater vulnerability.

The effects of parathyroid hormone (PTH), prostaglandins (PGE1, PGE2, PGF2a), cAMP, cAMP-analogues, phosphodiesterase (PDE) inhibitors and la (OH) D3 on bone resorption and associated cellular process have been studied in a bone organ culture system using half- calvaria from 6-7 day-old mice. Bone resorption was assessed by determining the release of calcium (Ca2+), inorganic phosphate (Pi) and 45Ca from the calvarial bones to the culture media. The release of lysosomal enzymes was studied by analysing the activities of β-glucuronidase, β-N-acetyl- glucosaminidase, β-galactosidase and p-nitrophenyl phosphatase in bone expiants and culture media. The release of non-lysosomal enzymes was followed by assaying the activities of lactate dehydrogenase (LDH), aspartate aminotransferase (ASAT) and alanine aminotransferase (ALAT) in the expiants as well as the media. In addition glucose consumption and lactate production was registered. The findings may be summarized as follows: 1. cAMP and PDE-inhibitors have the capacity to inhibit the initial stages of spontaneous as well as PTH- PGE1- and PGE2-stimulated bone resorption. 2. cAMP and PDE-inhibitors produce after a lag period, or a period of reduced bone resorption, a stimulatory effect on bone resorption. 3. There is a significant correlation between bone resorption and lysosomal enzyme release both as regards the inhibitory and stimulatory effect of cAMP. 4. PGE2 and la (OH) D3 increase the release of lysosomal enzymes in parallel with bone resorption. 5. Bone resorption stimulated by cAMP and PGE2 is associated with increased glucose consumption and lactate production, while la (OH) D3 promotes bone resorption without any change with regard to these parameters of glucose metabolism. It is concluded that the initial stages of bone resorption stimulated by PTH, PGE1 and PGE2 is medited by cAMP-independent mechanisms, but that this nucleotide may be an intracellular mediator of these hormones of later stages of bone resorption. It is suggested that the role played by cAMP may be related to the capacity of PTH and PGE2 to develop new osteoclasts. The observations further support the concept that lysosomal enzyme release is intimately associated with bone resorption. Finally it is concluded that increased lactate production seems to be related to bone resorption stimulated by agents which increase the level of cAMP (PTH, PGE2, dbcAMP), but that it is not an indispensible part of the mechanism by which the osteoclasts solubilize bone mineral. / digitalisering@umu.se

Philosophiae Doctor - PhD / Background: A subtype of inflammatory bowel disease, Crohn' s disease is thought to represent a complex interaction between environmental factors, a defective immune system, the gastrointestinal microbiome and genetic' susceptibility; however; the-prevalence of different susceptibility mutations appears to vary between population groups, implying distinctions in disease pathogenesis or risk. Vitamin D, signaling through the vitamin D receptor, appears to have numerous effects on the immune system, and deficiency has been shown to playa role in both the pathogenesis and severity of experimental inflammatory bowel disease. However, the literature surrounding the association between vitamin D concentrations and disease severity in Crohn's disease is limited, and no such literature exists in South Africa. Furthermore, a paucity of data exists on the racial variability of Crohn' s disease phenotype in the Western Cape population of South Africa, as well as environmental factors in childhood associated with future Crohn's disease development. Aims: The three primary aims of the study were to investigate: 1) the racial variability of, Crohn's disease phenotype, defined by the Montreal classification scheme, as well as Crohn's disease behavior, using predefined definitions, stratified as 'complicated' or 'uncomplicated', based on a cross-sectional study design; 2) the association between childhood environmental exposures and the subsequent development of Crohn's disease, with specific emphasis on the timing of exposure, based on a case-control study design; and 3) the association between serum 25(OH)D concentration with Crohn's disease activity, measured by the Harvey Bradshaw Index, based on a cross-sectional study design; in this process, various vitamin D thresholds for predicting a high disease activity score were investigated, and the serum 25(OH)D concentrations were compared with those of the healthy controls to evaluate the prevalence of vitamin D deficiency. Design: This was a case control study, as well as two cross-sectional evaluations of the case control study data, of all consecutive Crohn's disease patients (ages 18-70 years) seen between September 2011 and January 2013 during their normally scheduled appointments at Schuur Hospital and Tygerberg Hospital. Control subjects for the study were identified from the same populations giving rise to the Crohn's disease cases. An investigator-administrated questionnaire was used to identify numerous demographic and lifestyle variables, as well as childhood environmental exposures during three age intervals; 0-5, 6-10 and 11-18 years. Clinical variables at diagnosis and time of study enrolment were determined via a review of medical and pharmacy records, as well as clinical examination by the consulting gastroenterologist. Serum 25(OH)D was measured using the SIEMENS ADIVA Centaur® XP Vitamin D Immunoassay [Siemens Healthcare Diagnostics Inc., Tarrytown, NY, USA]. Vitamin D status was classified as either 'deficient' or 'sufficient', and was analyzed in 2 ways: ~20 ng/mL versus ~21 ng/mL; and ~29 ng/mL versus ~30 ng/mL, respectively. One year after study completion, a total of 40 (10%) randomly selected participants from the cohort completed the interviewer-administered questionnaire for a second time. A kappa statistic was used in order to measure the agreement between repeated data for the questionnaire. Only data pertaining to the three age intervals (0-5, 6-10 and 11-18 years) was extracted in this process. Results: One hundred and ninety four Crohn's disease patients and 213 controls meeting our inclusion criteria were identified; 35 (18%) and 19 (9%) were White, 152 (78%) and 177 (83%) were Coloured, and 7(4%) and 17 (8%) were South African Black, respectively. No subjects reported being of Asian or Indian ethnicity. Overall, 125 (31%) of the cohort were male. On multiple logistic regression analysis, Coloured Crohn's disease patients were significantly more likely to develop 'complicated' Crohn's disease (60% versus 9%, P = 0.023) during the disease course when compared to White Crohn's disease patients. In addition, significantly more White subjects had successfully discontinued cigarette smoking at study enrolment (31% versus 7% reduction, P = 0.02). No additional interracial differences were found. A low proportion inflammatory bowel diseases family history was observed among the Coloured and Black subjects. When evaluating childhood environmental exposures, multiple logistic regression analysis showed that during the age interval 6-10 years, never having consumed unpasteurized milk [(OR = 6.43; 95% Cl, 3.02-14.81), (K =0.79; 95% Cl, 0.39-1.00)] and never having a donkey, horse, sheep or cow on the property [(OR = 3.10; 95% Cl, 1.42-7.21), (K = 0.84; 95% Cl, 0.12-1.00)], significantly increased the risk of developing future Crohn's disease. During the age interval 11-18 years, an independent risk-association was identified for; never having consumed unpasteurized milk (OR = 2.60; 95% Cl, 1.17-6.10) and second-hand cigarette smoke exposure (OR = 1.93; 95% Cl, 1.13-3.35). For the vitamin Danalysis, 186 Crohn's disease patients and 199 control subjects met the study inclusion criteria. Overall, 113 (29%) of the cohort were male. Forty four percent of the cohort had a deficient vitamin D concentration (::;20 ng/ml.), no participants had severely deficient vitamin D concentrations, and 26% of the cohort had sufficient vitamin D concentrations (:::30 ng/mL). Fifty-three percent of the controls and 34% of the cases had vitamin D concentrations ::;20 ng/mL (P < 0.001). On multiple logistic regression analysis, higher Harvey Bradshaw Index scores and not having taken vitamin D supplementation in the six months prior to enrolment were identified as independent predictors of vitamin D deficiency in Crohn's disease patients; defined either as ::;20 ng/mL, or as ::;29 ng/mL (P < 0.001). Compared to patients with Harvey Bradshaw Index <5, those with Harvey Bradshaw Index 2:8 were 2.5-times more likely to have vitamin D concentrations ::;21 ng/mL (PR = 2.5; 95% Cl, 1.30-6.30). The risk was similar, though not as high, if deficiency was defined as ::;29ng/ml. (PR = 2.0; 95% Cl, 1.20-3.50). Conclusions: Coloured Crohn's disease patients were significantly more likely to develop 'complicated' Crohn's disease over time when compared to White Crohn's disease patients. Limited microbial exposures and exposure to second-hand cigarette smoke during childhood is associated with future development Crohn's diseases. However the inconsistencies between each age interval with regards to the identified risk factors may imply that the effect of different viruses or bacteria on the development of immune structures varies according to the timing of exposure. The finding that lower serum 25(OH)D was associated with moderate to severe Crohn's disease activity suggests that this patient population may benefit from vitamin D supplementation in order to achieve, or maintain a serum 25(OH)D concentration of at least 30 ng/mL.

The aim of this diploma thesis is a basic overview of system safety audit in the industrial enterprises with the application and evaluation of methodology of self audit in an industrial enterprises processed according to the Self-Audit Handbook for SMEs designed for small to medium-sized enterprises and to recommend measures to improve the occupational safety and health system.

This dissertation work deals with analysis of nickel hydroxide phases, their oxidation compounds, their stability and degradation mechanisms of electrochemically more active alpha phase on standard beta phase. The active material was prepared by both methods, electrodeposition and chemical precipitation. Main analysis method was Electrochemical Quartz Crystal Microbalance in combination with common analytical methods (cyclic voltammetry, potenciometry) can resolute between alpha and beta phases and quantitatively describe differences in main reaction by monitoring mass changes in the active material. Poor stability of the ?-Ni(OH)2 were improved by adding cations with valence two three and four into the structure instead of Ni atoms. The most important role plays cobalt and its hydroxide. Totally new way is to use titanium in combination with other cations. In electrolyte the most significant addition is LiOH, which has beneficial influent on cycle ability, stability in strong alkaline medium and cycle life.

Obsessive-compulsive disorder is a chronic psychiatric disease. It seriously limits the quality of life of patients. Treatment of OCD is not yet fully successful and still many patients are left with debilitating symptoms without functioning medication. Animal models of genetic, behavioral, pharmacological, and optogenetic origins are beneficial in the achievement of new understandings of the disease. Chronic sensitization of serotonin 1A and 7-receptors with an agonist 8-OH-DPAT ((8- hydroxy-2-(di-propylamino)-tetralin hydrobromide) induces perseverative and compulsive behaviors, which is considered to constitute an animal model of OCD. In this thesis, the 8-OH- DPAT model has been tested in the active place avoidance task on Carousel maze to provide information about the model on learning. Second, this model is used to determine, whether co- administration of memantine or riluzole alleviates the cognitive and learning deficits of this model. To uncover these effects, an active place avoidance task on a Carousel maze was used. Measured criteria were total distance, entrances to the shock sector, total number of shocks, and median speed after the shock. During habituation, the animals were sensitized to 8-OH-DPAT (with a control group that did not receive 8-OH-DPAT but only saline). In an...

Nitric acid has been implicated in a variety of physiological functions of the mammalian brain, and in a large number of its pathologies. Recently we have demonstrated that a nitric oxide donor (L-arginine) and a nitric-oxide-synthase-inhibitor (nitro-L-arginine-methyl-ester) modified the response of central al dopamine D 1 and D 3 receptors to some of their agonists. In the present study we demonstrate the modulatory effect of L-arginine, nitro-L-arginine-methyl-ester and molsidomine (another nitric oxide donor) on the reactivity of the central dopamine receptors to specific agonists and antagonists. The agonists tested were SKF-38393, 7-OH-DPAT and quinpirole, and the antagonists - SCH-23390 and haloperidol. They were evaluated in the rat by the following behavioral methods: locomotor activity, locomotor coordination, rearings and cataleptogenic activity (D 2 modulation); grooming time (D 1 activation); yawning (D 3 activation) and ethanol- and phenobarbital-sleeping-time parameters after SKF-38393 or quinpirole pretreatment. Our results suggest that nitro-L-arginine-methyl-ester is effective in modulating the reactivity of the central dopamine receptors D 2, D 1 and D 3, to their agonists and antagonists, and that it is much more effective than L-arginine in regulating the righting reflex after ethanol and phenobarbital, in both female and male mature rats.

Venom peptides are known to have strong antimicrobial activity and anticancer properties. King cobra cathelicidin or OH-CATH (KF-34), banded krait cathelicidin (BF-30), wolf spider lycotoxin I (IL-25), and wolf spider lycotoxin II (KE-27) venom peptides were found to strongly inhibit Escherichia coli membrane bound F1Fo ATP synthase. The potent inhibition of wild-type E. coli in comparison to the partial inhibition of null E. coli by KF-34, BF-30, Il-25, or KE-27 clearly links the bactericidal properties of these venom peptides to the binding and inhibition of ATP synthase along with the possibility of other inhibitory targets. The four venom peptides KF-34, BF-30, IL-25, and KE-27, caused ≥85% inhibition of wild-type membrane bound E.coli ATP synthase. Venom peptide induced inhibition of ATP synthase and the strong abrogation of wild-type E. coli cell growth in the presence of venom peptides demonstrates that ATP synthase is a potent membrane bound molecular target for venom peptides. Furthermore, the process of inhibition was found to be fully reversible.

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