INTRODUÇÃO: A redução automática da pressão de suporte (PS) baseada na freqüência respiratória, ou MRV (mandatory rate ventilation) é um modo ventilatório disponível no ventilador Taema-Horus. A hipótese do estudo é que o MRV utilizado no desmame é tão efetivo quanto o desmame manual em pacientes em pós-operatório na unidade de terapia intensiva (UTI). MÉTODOS: Ao chegar à UTI, após a cirurgia, os pacientes eram randomizados em dois grupos: desmame manual ou automático. O desmame manual consistiu na redução manual da PS a cada 30 minutos mantendo a relação freqüência respiratória sobre volume corrente menor do que 80, até a PS de 5-7 cmH2O. O desmame automático baseou-se na freqüência respiratória alvo de 15 respirações por minuto (o ventilador diminui automaticamente, a PS em 1 cmH2O a cada 4 ciclos respiratórios, se o paciente mantiver a freqüência respiratória abaixo deste valor). O objetivo primário do estudo foi comparar a duração do processo de desmame. Secundariamente verificamos o nível de PS, freqüência respiratória, volume corrente, índice de freqüência respiratória sobre volume corrente, pressão positiva expiratória final, fração inspirada de oxigênio e saturação de oxigênio requeridos durante o processo de desmame. Verificamos também necessidade de reintubação e necessidade de ventilação não invasiva nas primeiras 48 horas após a extubação. RESULTADOS: Não houve diferença estatística significativa entre os 53 pacientes selecionados em cada grupo quanto ao sexo (p=0541), idade (p=0,585) e tipo de cirurgia (p=0,172). Dezenove pacientes foram excluídos durante o protocolo (quatro no grupo manual e quinze no grupo automático, p<0,05). Nove pacientes do grupo automático foram excluídos do protocolo por não se adaptarem ao modo de desmame automático. Oitenta e sete pacientes concluíram o estudo, quarenta e nove pacientes foram desmamados manualmente e trinta e oito automaticamente. A duração do processo de desmame foi de 205,41±181,27 minutos (de 30 a 840 minutos) no grupo manual, e 157,33±129,98 minutos (de 30 a 545 minutos) no grupo automático. Não houve diferença estatística significante quanto ao tempo de desmame entre os dois grupos. O nível de PS foi maior (p<0,001) e freqüência respiratória foi menor (p=0,0098) no modo MRV comparado ao modo manual, durante o processo de desmame. Não houve necessidade de reintubação em nenhum dos grupos. Houve necessidade de ventilação não invasiva em dois pacientes do grupo manual (p=0,505), ambos sofreram cirurgia cardíaca. CONCLUSÃO: A redução automática da PS foi efetiva e pode ser utilizada no desmame de pacientes no pós-operatório na unidade de terapia intensiva, se o paciente se adaptar ao algoritmo do MRV / Introduction: Automatic pressure support reduction based on a target respiratory frequency or MRV is available in the TAEMA-HORUS ventilator for the weaning process in the ICU setting. We hypothesized that MRV is as effective as manual weaning in post-operative ICU patients. Methods: There were 106 patients selected, in the post-operative period in a prospective, randomized, controlled protocol. When the patients arrived in the ICU after surgery, they were randomly assigned to traditional weaning, consisted of the manual reduction of pressure support every thirty minutes, keeping the RR/TV(L) < 80 till 5-7 cmH20 of PSV. Alternatively, they were assigned to automatic weaning, referring to MRV set with a respiratory frequency target of 15 breaths per minute (the ventilator automatically decreased the PSV level by 1 cmH20 every 4 respiratory cycles, if the patients RR was less than 15 per minute). The primary endpoint of the study was the duration of the weaning process. Secondary endpoints were levels of pressure support, respiratory rate, tidal volume (mL), RR/VT (L), PEEP levels FiO2 and SpO2 required during the weaning process, the need for reintubation and the need for non-invasive ventilation in the 48 hours after extubation. Results: There were no statistically significant differences between the 53 patients selected for each group regarding gender (p=0.541), age (p=0.585) and type of surgery (p=0.172). Nineteen patients were excluded during the trial (4 in the PSV group and 15 in the MRV group, p<0.05). Eighty-seven patients concluded the study, forty-nine patients were weaned manually and thirtyeight automatically. The weaning duration process was 205.41 ± 181.27 minutes (30 to 840 minutes) for the manual group and 157. 33± 129.98 minutes (30 to 545 minutes) for MRV group (p=0.167). PSV levels were significantly higher and RR was lower in MRV compared to that of the PSV manual reduction (p<0.05). Reintubation was not required in either group. NIV was necessary for two patients, in the manual group after cardiac surgery (p=0.505). Conclusion: The automatic reduction of pressure support was effective and can be useful for weaning patients in the post-operative period in the ICU, if the patient is receptive to the MRV algorithm

The series of experiments described in this thesis were designed to investigate the role of suckling or late weaning in the response of young lambs to nematode infection. All experiments were conducted outdoors with grazing animals and no supplementation but for suckled groups of lambs whose counterparts were weaned to ryegrass – white clover swards. The parasite of interest was mainly Teladorsagia circumcincta solely but with mixed infection of Trichostrongylus colubriformis in one instance. In Chapter 3 (first experiment), the hypothesis that milk per se may have a direct effect on nematode development, rather than an indirect effect through enhancement of host immunity by superior nutrient supply was tested. Sixty, twinborn lambs were used, allocated to one of eight groups formed by either dosing lambs from 42 days of age or not with the equivalent of 1000 or 250 L₃ T. circumcincta larvae d⁻¹ until five days before necropsy, while a twin was either weaned at 39 days of age, suckled as single or twin until necropsy on day 84. The possibility that weaning one of a twin set onto pasture in close proximity to the ewe would cause abnormal ewe and lamb behaviour was tested by replicating the work in twins maintained as twins but in which one twin received equivalent of 250 and the other 1000 L₃ T. circumcincta larvae d⁻¹. This showed no abnormal ewe nursing or lamb suckling behaviour as a result of weaning a twin in a set. Relatively low faecal egg counts (FEC) and a two to three fold lower worm burdens suggest suckling could reduce larval establishment. Inability to detect peripheral titres of immunoglobulins supports this conclusion. An intra worm-population regulation of T. circumcincta, indicated by a pattern of greater egg-laying by a numerically smaller but physiologically better developed nematode population in suckled lambs measured in eggs 'in utero' and worm length made interpretation of FEC difficult. Suckling significantly improved weight gain and carcass weights, but early weaning did not reduce resilience to infection. In Chapter 4 (second experiment), 40 pairs of twin lambs, average age of 39 days, were either infected with the equivalent of 1000 L₃ T. circumcincta larvae d⁻¹ or not, while one twin was weaned and the other allowed to continue suckling. Necropsy was carried out on groups of five and six lambs from each of the uninfected and infected treatments, respectively, at mean age of 84, 112, and on six lambs from each group at 140 days of age. This serial slaughter allowed further confirmation of the hypothesis in Chapter 3 but also investigated the long-term effect of suckling on resistance or resilience of lambs at the trial when immune responses were anticipated to be developing. An in vitro direct larval challenge (IVDC) study, to monitor larval establishment, was carried out on tissue explants from necropsied lambs. Suckled lambs consistently showed lower FEC (P < 0.05) and worm burdens (P < 0.05) at every phase of the trial. Within the infected groups, % in vitro larval rejection suggested earlier immune responses in the weaned lambs by day 84, which was not consistent with lower worm burdens in suckled lambs but appeared similar in the subsequent necropsies. Lambs continued to show better growth due to suckling while weaning did not reduce the resilience of lambs confirming observations in Chapter 3. The immunoglobulin profile suggested the commencement of immune responses in lambs from the period after the 84th day necropsy, with significantly greater (P < 0.01) IgA titre in the infected groups, and the suckled lambs towards the end of the trial on day 140. A vaccinating effect of early exposure to parasites was coincidentally revealed as a result of unintentional pasture larval contamination, seen in suckled non-infected lambs shedding fewer eggs and harbouring fewer worms during the later necropsies compared with their weaned non-infected counterparts. In Chapter 5 (third trial), 93 pairs of twin lambs, 47 pairs of which received a vaccinating mixed infection of T. circumcincta and T. colubriformis larvae (60 L₃ / kg W / d) at ratio 40:60, respectively during the period 36 – 103 days of age, were either weaned early on day 51 or later on day 108. All lambs were drenched on day 108 and groups received challenge infections from day 116, at same rate with the vaccinating infection, or not, which ceased five days before respective necropsies. Necropsies were carried out on selected lambs on days 108, 184 and 218. The direct effect of milk on larval establishment appeared to feature only in the T. circumcincta populations on slaughter day 108. The long-term benefit of late weaning for development of resistance was conditional on lambs receiving the vaccinating infection, and appeared to be more pronounced in the small intestine, reflected by a greater reduction of T. colubriformis populations in that organ than of T. circumcincta populations in the abomasum. A negative consequence of enhanced immune response was the suggestion of an increased metabolic cost in reduced performance of lambs. In conclusion, the work provides support to the hypotheses that: (a.) suckling may reduce the establishment of nematode larvae through the direct effect of milk, (b.) may enhance rapid development of host immunity to infection, and (c.) it further suggests that lack of larval experience during suckling may have long term negative implications for host resistance. Finally, it suggests that milk may play little role in the enhancement of host resilience to infection and, on the contrary, that additional metabolic cost may be associated with a more rapid development of immunity resulting from larval challenge while suckling.

<p>This study, based on daily recordings of infant feeding, comprised 506 infants from Uppsala, Sweden. All mothers had had previous breastfeeding experience of at least 4 months, and were planning to breastfeed the index child for ≥6 months.</p><p>Among exclusively breastfed infants there were wide variations in breastfeeding frequency and suckling duration per 24 hours both between infants and in the individual infant over time in the first 6 months. Most infants had an average of 1.0-2.9 feeds per night. Infants using a pacifier had fewer feeds and a shorter total suckling duration per 24 hours, and stopped breastfeeding earlier than infants not using a pacifier. These associations were not found for thumb sucking.</p><p>Accustoming the infants to solids was a lengthy process, the longer the younger the infant at introduction, and was associated with small changes in pattern and duration of breastfeeding. In contrast, formula was usually given in large amounts from the beginning, and when formula was given regularly the daily breastfeeding frequency and suckling duration declined swiftly. The younger an infant at the start of regular formula feeds, the shorter the breastfeeding duration. Occasional formula feeds did not affect the breastfeeding duration.</p><p>It is important for health personnel and parents to keep in mind that exclusively breastfed infants are not a homogeneous group, but rather members of distinct 'breastfeeding entities'. Moreover, if the aim is to introduce other foods 'under the protection of breast milk' it is important to realise that formula is also 'another food' and needs to be treated as such.</p>

This study, based on daily recordings of infant feeding, comprised 506 infants from Uppsala, Sweden. All mothers had had previous breastfeeding experience of at least 4 months, and were planning to breastfeed the index child for ≥6 months. Among exclusively breastfed infants there were wide variations in breastfeeding frequency and suckling duration per 24 hours both between infants and in the individual infant over time in the first 6 months. Most infants had an average of 1.0-2.9 feeds per night. Infants using a pacifier had fewer feeds and a shorter total suckling duration per 24 hours, and stopped breastfeeding earlier than infants not using a pacifier. These associations were not found for thumb sucking. Accustoming the infants to solids was a lengthy process, the longer the younger the infant at introduction, and was associated with small changes in pattern and duration of breastfeeding. In contrast, formula was usually given in large amounts from the beginning, and when formula was given regularly the daily breastfeeding frequency and suckling duration declined swiftly. The younger an infant at the start of regular formula feeds, the shorter the breastfeeding duration. Occasional formula feeds did not affect the breastfeeding duration. It is important for health personnel and parents to keep in mind that exclusively breastfed infants are not a homogeneous group, but rather members of distinct 'breastfeeding entities'. Moreover, if the aim is to introduce other foods 'under the protection of breast milk' it is important to realise that formula is also 'another food' and needs to be treated as such.

Una dieta scorretta incrementa il rischio di malattie come l’insulino resistenza e l’obesità. Questa tesi ha l’obiettivo di valutare l’effetto di diete sbilanciate sulla fisiologia ed espressione genica in topi e suini allo svezzamento. Topi C57BL/6 sono stati sacrificati dopo 2 settimane, dopo essere stati alimentati con dieta iper-lipidica e dieta controllo. L’espressione genica è stata stimata usando la tecnologia microarray. Quattro dei sette geni identificati differenzialmente espressi tra il controllo e l’iper-lipidico sono coinvolti nella regolazione della via metabolica del sistema circadiano, che recentemente è stato mostrato avere effetti sul metabolismo lipidico e processo infiammatorio. Il secondo studio ha avuto lo scopo di capire gli effetti dello svezzamento con o senza l’aggiunta di acidificante nella dieta. I suinetti allo svezzamento (T0) sono stati comparati con i suinetti dopo una settimana (T1). Il gruppo post-svezzamento è stato alimentato con una dieta convenzionale, e metà di questi hanno ricevuto un supplemento di acido sorbico. L’aggiunta di acido sorbico nella dieta non ha causato nessuna differenza a livello fisiologico e di espressione genica. 205 geni sono stati identificati come differenzialmente espressi in T1 comparato con T0, evidenziando una forte risposta all’adattamento metabolico e agli stress subiti durante lo svezzamento. / An incorrect diet increases the risk of diseases as insulin resistance and obesity. This thesis aims at assessing the effects of unbalanced diets on gut physiology and gene expression in pig and mouse during weaning. The first research explored the impact of a high fat diet in C57BL/6 mice. High-fat-fed mice and control-fed mice were sacrificed after two weeks of treatment. Gene expression level was assessed by 90K Combimatrix microarray technology. Four of seven genes found differentially expressed between control and high fat diet mice are involved in the regulatory pathway of the circadian clock system, which was recently shown to affect lipid metabolism and inflammatory processes. Those genes were successfully validated by real time PCR. The second study aimed at understanding the weaning effect with or without acidifier addition in the diet. Piglets at weaning (T0) were compared to piglets after one week (T1). The post-weaning group was fed a conventional diet, half of which received in addition sorbic acid. The sorbic acid supplementation evidenced no effects in terms of physiology and gene expression. 205 genes were significantly differentially expressed in T1 when compared with T0, evidencing a response to the metabolic adaptation and the stress suffered during weaning.

In der vorliegenden Arbeit wurde die Bedeutung des Einflusses von Laktationsnummer, Laktationsstadium, Körperkondition und Absetzverfahren auf Merkmale der Milchleistung und Eutergesundheit einer Herde Ostfriesischer Milchschafe untersucht. Die Tiere wurden nach dem Ablammen zufällig einer Früh- bzw. Spätabsetzergruppe zugeordnet (Absetzen der Lämmer 3 bzw. 42 Tage post partum). An insgesamt 40 Terminen wurden über eine vollständige Laktation Vorgemelks-, Hälftenanfangsgemelks- und Einzeltiergemelksproben gewonnen. Das Spektrum der untersuchten Merkmale umfasste die Milchmenge, die Milchinhaltsstoffe (Fett, Eiweiß, Laktose), die klinische Untersuchung des Euters, die somatische Zellzahl, die elektrische Leitfähigkeit und bakteriologische Untersuchungen. Zusätzlich wurden das Körpergewicht und die Körperkondition der Mutterschafe erfasst. Das durchschnittliche Leistungsniveau der Herde betrug 301±101,3 kg Milch, bei mittleren Milchfett-, Milcheiweiß-, und Laktosegehalten von 5,00, 5,14 bzw. 5,00 % (150-Tageleistung). Die Laktationsnummer hatte keinen signifikanten Effekt auf die Milchleistung. Schafe der Spätabsetzer-Gruppe produzierten im Anschluss an die Säugephase eine um 300 g signifikant höhere Testtagsmilchmenge als Tiere der Frühabsetzer-Gruppe. Das Absetzverfahren hatte keinen nachweisbaren Effekt auf die Milchinhaltsstoffe. Die Herde wies eine gute Eutergesundheit auf. Der Anteil bakteriologisch positiver Schafmilchproben betrug 28,5 %. Als dominante Erreger wurden in 96,6 % der bakteriologisch positiven Schafmilchproben Koagulasenegative Staphylokokken nachgewiesen. Der Anteil bakteriologisch positiver Euterhälftenbefunde stieg signifikant mit dem Fortschreiten der Laktation und zunehmender Laktationsnummer. Eine Euterinfektion mit Koagulasenegativen Staphylokokken sowie das Verfahren des Spätabsetzens beeinflussten alle drei untersuchten Eutergesundheitsparameter (logarithmierte Zellzahl, elektrische Leitfähigkeit und Laktosegehalt) negativ (p < 0,001).

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Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro / O cálcio tem se mostrado útil na regulação do metabolismo energético, favorecendo a perda de peso. Visto que tanto o desmame precoce como a exposição materna à nicotina na lactação são fatores condicionantes para o desenvolvimento de obesidade, hiperleptinemia e resistência à insulina, além de outras alterações endócrinas na idade adulta, decidimos avaliar os possíveis efeitos da suplementação dietética com cálcio sobre as disfunções apresentadas pelos seguintes modelos experimentais: 1) Desmame precoce (DP): ratas lactantes foram envolvidas com atadura para interromper o acesso da prole ao leite nos 3 últimos dias da lactação. As proles das ratas controles tiveram livre acesso ao leite materno durante todo o período da lactação (21 dias). 2) Exposição materna à nicotina (N): Dois dias após o nascimento, ratas lactantes receberam implantes de minibombas osmóticas contendo solução de nicotina (6 mg/kg/dia, 14 dias) ou salina (C), nas mesmas condições. Aos 120 dias de idade, as proles de ambos os modelos de obesidade experimental receberam dieta padrão ou dieta suplementada com cálcio (10g de carbonato de cálcio/kg de ração). O sacrifício ocorreu aos 180 dias de idade. Os dados foram considerados significativos quando p<0,05. Corroborando dados anteriores do nosso grupo, as proles de ambos os modelos de programação (N e DP) apresentaram maior gordura corporal total e visceral, hiperleptinemia, resistência hipotalâmica a leptina e distúrbios na homeostase glicêmica. Além disto, verificamos que as proles N e DP também exibiram aumento dos níveis séricos de 25-hidroxivitamina D3. Todos essas alterações endócrino-metabólicas foram corrigidas pelo tratamento com suplementação com cálcio. Além disso, a prole DP aos 180 dias mostrou hiperfagia e hipertrigliceridemia, que também foram normalizados pela suplementação dietética com cálcio. A prole N apresentou hipotireoidismo, maior conteúdo de catecolaminas e maior expressão de tirosina hidroxilase (TH). A terapia com cálcio reverteu a disfunção adrenal, embora não tenha sido eficaz para normalizar a hipofunção tireoideana. Assim, a suplementação dietética com cálcio normalizou a maioria dos parâmetros da síndrome metabólica observadas nos dois modelos de plasticidade ontogenética. É possível que a redução da adiposidade central induzida pela terapia com cálcio, por si, tenha sido o principal mecanismo que resultou na melhora dos parâmetros estudados. Uma vez que a suplentação de cálcio reverteu as concentrações séricas de 25-hidroxivitamina D3 dos animais obesos, é possível que o efeito anti-obesidade do cálcio também ocorra via ação do calcitriol sobre o adipócito. / Calcium influences energy metabolism regulation and causes body weight loss. Since early weaning and maternal nicotine exposure during lactation programs for obesity, hyperleptinemia, insulin resistance and others endocrine dysfunctions, we studied the possible effect of dietary calcium supplementation on endocrine dysfunctions in these two experimental model of obesity: 1) Early Weaning (EW): lactating rats were involved with a bandage to interrupt the lactation during the last 3 days of standard lactation, and C (control) - dams whose pups had free access to milk during all lactation (21 days). 2) Maternal nicotine exposure (N): Two days after birth, it was implanted on the mothers, osmotic minipumps containing nicotine solution (6 mg/Kg/day, 14 days) or saline (C) in the same condition. At 120 days-old, all offspring received dietary calcium supplementation (10g of calcium carbonate/Kg of rat chow) or standard diet. Rats were killed at 180 days-old. Significant data were p<0.05. As expected, N and DP offspring showed higher visceral and total body fat mass, hyperleptinemia, hypothalamic leptin resistance and insulin resistance. In addition they presented higher serum 25-hydroxyvitamin D3. All these disturbances were corrected after calcium supplementation. Besides, adult EW offspring displayed hyperphagia and hypertriglyceridemia that was normalized with calcium therapy. Also, N offspring presented hypothyroidism, higher tyrosine hydroxylase expression and higher adrenal catecholamine content. Despite calcium treatment have normalized adrenal dysfunction, it did not reverse the hypothyroidism. So, dietary calcium supplementation seems to revert most of the metabolic syndrome parameters observed in our two developmental plasticity models. It is conceivable that the reduction in fat mass per se, induced by calcium therapy, is the main mechanism that improves all parameters. Because serum 25-hydroxyvitamin D3 levels were corrected by calcium supplementation in obese offspring, it is possible that the anti-obesity effect of calcium occurs through calcitriol action on the adipocyte.