By A. Spike. Springfield College. 2018.

In animal cells 500 mg naprosyn visa, two major pathways are com- monly described for apoptosis; the death-receptor pathway naprosyn 500 mg generic, referred to as the extrinsic pathway, and the mitochondrial route. Both pathways lead to caspase (cysteine proteases that their substrates following specifc aspartate residues) activation and cleavage of their specifc substrates. Therefore, members of Bcl-2 family are regarded as key elements in maintaining a balance between cell growth and cell death. It is believed that in animal cells, apoptosis is controlled by an equilibrium between antiapoptotic and proapoptotic members. For ex- ample, a high level of Bcl-2 relative to Bax promotes survival, while an excess of Bax results in cell death. Pro- and antiapoptotic Bcl-2 members are known to interact with each other at the level of protein–protein interactions; such interaction may play a regulatory role in the induction or the suppression of cell death. Among them, the Bax protein can promote apoptosis by interfering with mitochondria features either by forming a channel leading to the release of the electron transfer protein, cytochrome c, or by perturbing the oxidative state. Several other factors, such as post-translational modifcations, may also regulate the fnal cellular outcome. Accordingly, some reports have suggested the importance of Bcl-2 phosphorylation [4]. Since killing cancer cells remain a signifcant topic, the scope of this paper is to review the known effects of plant antitumoral substances on apoptosis. Alternatively, other substances known as chemopreventive agents have low toxicities com- pared to the chemotherapeutic agents, but they appear promising for prevent- Chapter 17 Apoptosis and Plant-Derived Pharmaceuticals 319 ing, arresting, and reversing cancer [5]. Among the most studied antitumoral drugs fgure: (1) the taxanes, (2) the vinca alkaloids, (3) the lapachone, (4) the polyphenol derivatives, and 5) the catechin derivatives from tea plants. Among these substances, the taxanes appears to be the broadest, in terms of antitu- mor spectrum, of any class of anticancer agents. Taxanes are diterpenes that are produced by plants of the genus Taxus, known also under the name of yews. Paclitaxel (commercialized under the name of taxol), initially extracted from the bark of a Pacifc yew tree known as Taxus brevifolia, and docetaxel (commercialized as taxotere), derived from the needles of the English yew, are the two commercialized taxoid drugs. The vinca alkaloids, principally the two natural compounds vinblastine and vincristine and the semisynthetic deriva- tives vindesine and vinorelbine, have been used as anticancer drugs for more than 30 years. The lapachone extracted from the bark of lapacho tree is a form of quinone that is quite attractive since its action may be specifcally targeted at cancer cells. Besides these chemotherapeutic drugs, several studies have high- lighted natural compounds that act as chemopreventive agents, which were discovered following epidemiological observations revealing a low cancer in- cidence in populations drinking tea or those eating soyfood, fruits, vegetables, faxseed, peanuts, grapes, and/or red wine, suggesting the presence of cancer protective agents. Several mechanisms to explain the benefcial effects of plant-antitumoral substances have been proposed, among which their effects on target-specifc cell-signaling pathways regulating cell growth and proliferation as well as apop- tosis have been quite extensively studied. However, the exact mechanism(s) underlying the effects of these compounds on apoptosis remains unclear. The effects of several substances including the taxanes and vinca alkaloids on mi- crotubules have been frequently documented (see [7] and references therein). It is believed that these antimicrotubule agents can induce not only mitotic ca- tastrophe, but could also activate cell death. On the other hand, several studies have shown a correlation between plant-drug-induced cell death and expression of apoptotic regulators or altered signaling pathways. Taxanes bind to B-tubulin and promote their polymerization, interfering then with the function of the mitotic spindle, which leads to cell cycle growth arrest [8]. In addition to their effect on the cell cycle, several studies have documented 320 L. The taxane-induced effect on apoptosis could be related to their action on the cy- toskeleton. Accordingly, since the cytoskeletal network is important for mito- chondrial arrangement, one could speculate that taxanes initiate an apoptotic pathway by interfering with either the extrinsic apoptotic pathway or with mi- tochondrial function by facilitating the release of cytochrome c or by perturb- ing oxidative intracellular stress [15–18]. Alternatively, taxane-induced apop- tosis could interfere with some members of the regulatory proteins belonging to the Bcl-2 family. Although controversial, the signifcance of Bcl protein phosphorylation also highlights the involvement of diverse kinases such as protein kinase A, mitogen-activated protein kinase, or Raf kinase, within the biochemical events leading to apoptosis [20–23]. The ectopic expression of the proapoptotic protein Bax or Bad has been shown to sensitize cancer cells to paclitaxel and induce apoptosis [24, 25]. It has been proposed that taxol may increase cellular susceptibility to apop- tosis by amplifying the normal downstream events associated with mitotic ki- nase activation [26]. In addition to the downregulation of Bcl-2, several authors considered that upregulation of p53 and p21 are important for taxane-induced apoptosis, depending on the cellular context [27, 28]. Accordingly, cells lacking p53 or cells from p-53-null mice display increased sensitivity to paclitaxel [29, 30]. However, as demonstrated by the team of Tan [28], low doses of paclitaxel induce apoptosis through the upregulation of p53, while the death induced by higher concentrations occurred in a p53-independent manner, pinpointing the complexity of cellular equilibrium [28]. As complex as the situation described above for taxoid compounds, alkaloids may act at different levels of the death pathway Chapter 17 Apoptosis and Plant-Derived Pharmaceuticals 321 in numerous cell types, and the mechanisms by which vinca alkaloids induce apoptotic cell death in tumor cells is not clearly defned.

However order naprosyn 500mg with visa, using the vacuum for head rotation should be avoided due to its high risk of scalp laceration cheap 250 mg naprosyn with amex. Finally, the forceps delivery should be reserved to skilled birth attendants; specially the forceps rotations (Kjelland or Scanzoni maneuvers). If all these options fail to succeed or are found to be contraindicated, a caesarean section should be performed. The fetus presents its largest head diameter (occipitomental), which is increased 3 cm over flexed head (24%). The main causes are grand multiparous, large fetus and contracted pelvis, neck swelling (cystic hygroma or thyroid goiter) and anencephaly. A differential diagnosis should be made with the breech presentation, much more common than the face. In the management of this situation, one should never attempt to convert face presenta- tion to vertex. In general, vaginal delivery is possi- ble in mentum anterior (face anterior) and brow (0,02%) not converted to face or occiput (figure 1). However, mentum posterior or face posterior are an indication for caesarean section (figure 2). At the vaginal digital exploration, the hand is easily palpated beside the fetal head. When the fetus is transverse with the back down, the shoulder sits over the pelvic inlet (shoulder presentation). The most frequent causes are prematurity, placenta previa, ab- normal uterus, contracted pelvis or relaxed abdominal wall, and the presence of polyhidramnios, The diagnosis may easily be made by Leopold’s maneuvers. An external cephalic version may be at- tempted, as long as the membranes are intact and there is no labour. The signs of breech presentation are: a) Leopolds’ maneuvers: longitudinal fetal lie, being the head palpated in the uterine fun- dus, although it may be obscured by maternal ribs. Before labour, there is a higher risk of premature rupture of membranes and cord prolapse. The management of the breech presentation requires an evaluation for the possible causes of the situation. In case of failure, according to the operator’s experience, a vaginal delivery or a caesarean section should be performed. In footling or incomplete breech, a caesarean section should be indicated the indications for caesarean section should be liberal (table 1). The indications for cesarean section should be liberal: • Pelvis contraction or nongynecoid pelvis. The contraindications are: pregnancy induced hypertension, prior uterine surgery (e. The position of the mother is supine, Trendellenburg and with the knees slightly bent; in order to help breech fetus to rise above the pelvic brim. Once the fetus has rotated past the transverse lie, the examiners hands push the fetus into vertex position. The procedure should be stopped if the mother feels sharp pain, there is no success after 20 minutes or a fetal bradicardia appears. If such bradicardia persists, one should return the fetus to its original breech position. The most frequent reasons for failed procedure are fetal macrosomia, olygoamnios, fully extended position of the fetus, fetal malformations, short umbilical cord, anterior placen- ta, nulliparity, obesity, or gestational age of 37 weeks or more. The most common complication is the fetal bradicardia or fetal heart rate decelerations. Some rare, serious complications are partial placental abruption, uterine rupture, umbilical cord accident, or amniotic fluid em- bolism. In most cases, nothing should be done until the inferior angle of the scapulas appear. The complete spontaneous delivery is uncommon in nulliparous women and might take too long, jeopardizing the fetus wellbe- ing. Delivery of a fetus in breech position by extending the legs and trunk of the fe- tus over the pubic symphysis and abdomen of the mother, which leads to the spontaneous delivery of the fetal head (figure 5 and 6). If the shoulders cannot be exteriorized, the Deventer-Müller ma- neuver should be performed. The fetus needs to be rotated until its biacromial plane is parallel to the mother’s sagital plane. Then it is stretched downwards until the anterior shoulder appears and the arm is exteriorized. The posterior shoulder is then converted to anterior and the second arm is liberated (figure 6).

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Patients at the extremes of age and those who are immunosuppressed may have atypical examination find- ings generic naprosyn 500 mg without prescription. In these patients discount naprosyn 500 mg fast delivery, tachypnea may be the most sensitive sign of pneumonia A chest x-ray is an important diagnostic tool in patients with suspected pneu- monia as pulmonary infiltrates will confirm the diagnosis. In some cases, a patient with an initial negative chest radiograph may have infiltrates that “blossom” after rehydration or that are visualized using other types of imaging (eg, computed tomography is more sensitive than plain x-ray). The radiographic appearance of the infiltrates may suggest (but not definitively identify) a possible etiologic organism. Staphylococcus aureus, Pseudomonas, and Haemophilus influenzae typically cause mul- tilobar disease. Patchy infiltrates are consistent with Legionella, Mycoplasma, and chlamydial infection. Aspiration pneumonias usually result in infiltrates in depen- dent areas of the lungs (posterior segment of upper lobe or superior segment of lower lobe). Cavitary lesions, pleural effusions, and pneumatoceles may also be seen with bacterial pneumonias. Immunocompromised patients are especially likely to have atypical radiographic findings (eg, more diffuse or multilobar infiltrates). Treatment The initial management of patients with pneumonia includes assessment and, if needed, cardiopulmonary stabilization which may require supplemental oxygen or intubation for patients with severe respiratory distress or respiratory failure. Antibiotics should be initiated promptly in order to decrease mortality and improve patient outcome. Antibiotics are usually chosen based on the most likely pathogens as determined by assessment of risk factors, clinical presentation (including severity of symptoms and presence of sepsis), and radiographic find- ings. Patients with comorbid diseases or recent antimicrobial use should receive a respiratory fluoro- quinolone (levofloxacin) or a β-lactam (cefpodoxime) plus a macrolide as a rea- sonable alternative. A β-lactam (ceftazidime) plus either azithromycin or a fluoroquinolone may be used. If concern for aspiration pneumonia consider anaerobic coverage such as clindamycin. Disposition Factors to be considered include patient’s age and comorbidities, physical examination and diagnostic findings, ability to tolerate oral medications, social situation, and ability to obtain close follow-up. Obviously, any patient with unstable vital signs, respiratory distress, hypoxia, severe infection, or intractable vomiting requires a hospital stay. Examination reveals poor dentition with halitosis, coarse breath sounds, and clubbing of his fingers. On chest x-ray, there is a 2-cm cavitary lesion with an air-fluid level in the right lower lobe. The history of alcoholism, presence of periodontal disease, duration of illness, symptoms and signs, and radiographic findings suggest an anaerobic source. She has no risk factors for drug-resistant Streptococcus pneumonia nor any indications for admission. This patient is a candidate for inpatient treatment due to his comorbidities and abnormal vital signs. Although these are all appropriate interventions, this patient has signifi- cant hypoxia and respiratory distress despite noninvasive supplemental oxygen administration. Patients at the extremes of age and those immunocompromised may present atypically (clinically as well as radiographically). The chest x-ray is usually the most important diagnostic study in patients with suspected pneumonia. Empiric antibiotics are chosen based on the most likely pathogens (as determined by assessment of risk factors, clinical presentation, and radiographic findings). Factors to be considered when determining need for admission include the patient’s age and comorbidities, physical examination and diagnostic findings, ability to tolerate oral medications, social situation, and ability to obtain close follow-up. Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. Infectious Diseases Society of America/American Tho- racic Society consensus guidelines on the management of community-acquired pneumonia in adults. Guidelines for the management of adults with commu- nity-acquired pneumonia: diagnosis, assessment of severity, antimicrobial therapy, and prevention. Evidence-based medicine: empiric antibiotic therapy in community-acquired pneumonia. The patient relates a 3- to 4-day history of dark, tarry stools (about 3-4 times per day). He denies any hematemesis, hematochezia, chest pain, shortness of breath, and any similar past episodes.

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Prevalence of anti-infective use before pregnancy buy generic naprosyn 500 mg on line, during the first 250mg naprosyn sale, second and third trimester, stratified by drug class. Class of Anti- Number of Number of Number of Number of infectives prescriptions prescriptions prescriptions prescriptions (Percentages may not add and percent and percent and percent and percent up to 100% due to rounding. Groups are not mutually exclusive since a woman could have received more than one class of anti- 12 months First Second Third infective. Manuscript submitted to the Journal of Population Therapeutics and Clinical Pharmacology 2012. Overuse of broad spectra antibiotics is associated with development and spread of bacterial resistance, a problem that is faced as a significant threat to the public health. Objectives: To describe trends in use of general and broad spectrum anti- infective drugs during pregnancy. Methods: We used the Quebec Pregnancy Registry to analyse trends for use of oral anti-infectives dispensed during pregnancy for the five-year period comprised between January 1998 and December 2002. Trends in use were assessed for classes of anti-infectives and for broad-spectrum drugs. Descriptive statistics were used to summarize the characteristics of the study population. Annual trends for anti-infective use were analyzed using the Cochran-Armitage test. Results: The use of anti-infective drugs and broad spectrum agents during pregnancy decreased from 1998 to 2002 (p ≤ 0. The classes that showed increasing trend for use were: macrolides, quinolones, tetracyclines, urinary anti-infective drugs and antimycotics. Conclusions: Decrease of broad-spectrum anti-infective drugs use may have been caused by a positive impact of data issue from evidence in everyday life 125 clinical practice. More data are needed to evaluate the impact of the knowledge transfer from evidence-base studies on prescription’s trends during pregnancy. Healthy pregnant women are no more susceptible to most infections than their non- pregnant counterparts. However, when an infection occurs during pregnancy, it can be associated with obstetric complications, and physicians can be reluctant to prescribe anti-infectives since some antibiotics (e. On the other hand, the use of antibiotics in pregnancy has been cited as one of the main causes of decrease in maternal and perinatal mortality in industrialized countries (3). An important issue related to the use of such drugs during pregnancy is the choice of an effective therapeutic regimen in situations where resistant infections are life-threatening. However, the development of knowledge in understanding the use of broad spectrum antibiotics during pregnancy has been in stalemate in comparison to other areas of therapeutics, due mainly to difficulties in testing medications in pregnant women and lack of good evidence-based data (5). Use and overuse of broad spectra antibiotics is associated with development and spread of bacterial resistance, a problem that is faced by health care organizations as a significant threat to the public health. In this study, we describe trends in prescription of general and broad- spectrum anti-infective drugs during pregnancy in the province of Quebec, Canada, over a period of five years. Data sources The study was conducted using the Quebec Pregnancy Registry, which contains data on all pregnancies with drug plan coverage occurring in Quebec between January 1st 1998 and December 31 2002. MedEcho database furnish procedure codes related to pregnancy, including a planned or spontaneous abortions or deliveries (live births or stillbirth). The final Quebec Pregnancy Registry has often been used to assess the risks and benefits of drug use during pregnancy (10). Trends in anti-infective drugs use We analysed trends for new prescriptions of oral systemic anti-infectives dispensed during pregnancy for the five-year period comprised between st st January 1 1998 and December 31 2002. Statistical analysis Descriptive statistics were used to summarize the characteristics of the study population and to compare anti-infective use during pregnancy according to calendar year. Prevalence of anti-infective drug use during pregnancy for each year was calculated by dividing the number of women filling at least one prescription for an anti-infective drug in each 12-month period by the total number of women that met eligibility criteria for that year. Prevalence of use for each class and individual molecule was calculated by dividing the total number of new prescriptions for each class/type of anti-infective by the total 130 number of filled prescriptions for a giving period. Annual trends in anti- infective prescriptions were analyzed using the Cochran-Armitage test for trend. There were 34753 filled prescriptions for anti-infective drugs during the five-year period considered: 33510 were new filled prescriptions (3. The overall use of anti-infective drugs during pregnancy decreased from 1998 to 2002 (p ≤ 0. The same result was found when the analysis considered the use of broad spectrum agents; for this class, the highest prevalence of use was observed in 2000: 38. The classes that showed increasing trend for use were: macrolides, quinolones, tetracyclines, urinary anti-infective drugs and antimycotics. Use of penicillins and sulfonamides decreased, while cephalosporins, anti-protozoals and antimycobacterials showed no trend.

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