Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications.

Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiff's base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli-responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli-responsive linkage.

[Antineoplastic profile assessment for the evaluation of occupational exposure in hospital personnel involved in handling cytotoxic agents]. / Definizione del profile di chemioterapici antiblastici nella valutazione dell'esposizione professionale in ambito sanitario.

Environmental and biological monitoring performed in health care settings during a 14-year period allowed numerous data to be obtained by using the HPLC coupled with tandem mass spectrometry (HPLC-MS/MS). Data was stored in a specific data-base for the assessment of risk exposure to antineoplastic agents (CA). The strategy of analysis was based on the simultaneous determination of different active substances with a lower limit of quantification (LOQ) optimized in the range of sub-units of microg/L. In the present study, the MRM-ESI-MS/MS profiles of seven antineoplastic agents in both environmental and biological matrices are reported. These methods validated according to FDA guidelines allowed our lab to define a profile of antineoplastic agents that was representative of the four IARC classes, such as cyclophosphamide (group 1), cisplatin and doxorubicin (group 2A), daunorubicin (group 2B), 5-fluorouracil, ifosfamide (group 3), taxol, and gemcitabine (group 4). Moreover, contamination levels on a number of work surfaces and trends over a 14-year period are presented. The evaluation of occupational exposure to CA has been based on ALARA principle for most of the past decades but this principle is nowadays overwhelmed by the fast development of technology. The assessment of a possible in-take of CA in hospital personnel, when the sources of environmental contamination are identified, has become possible by the defining of a limit of exposure close to the limit of detection of the analytical method.

[Reference values for 42 trace elements in biological fluids (database RE-VA)]. / Valori di riferimento di 42 elementi in traccia in fluidi biologici della popolazione generale (database RE-VA).

The increasing use of multi-elementary techniques such as inductively coupled plasma mass spectrometer (ICP-MS), possibly in combination with dynamic reaction cell or other device, has greatly simplified the determination of trace elements in serum or plasma, whole blood and urine, even resorting to a phase of mineralization of the sample with microwave and teflon pressurized containers. This has made it necessary, however, an accurate control of interference, particularly polyatomic, using when possible, high-resolution ICP-MS, ICP-OES and ETA-AAS with electrothermal atomization. RE-VA study involved 162 subjects and has made available the reference values or background values for 42 elements in the matrix above. Physiological variables, life habits and food were also investigated. The aim is to implement the series through the sampling and analysis of similar types of samples in other Italian regions and countries in Europe and beyond. The data obtained allow to focus any inconsistencies for specific analytes and matrices, in order to identify critical variable attributable to both analytical and pre-analytical factors. For elements such as W, Ba, Cs, Pt, RE-VA study has revealed significant differences compared to other studies, and this is most likely to report high analytical sensitivity of DRC-ICP-MS as confirmed by comparative studies with Sector Field ICP-MS which provided matching values. It is also discussed the limitation of the use of VR for studies aimed at population groups living in industrial areas or where there are landfills, coal power plants and thermo incinerators.

[Determination of persistent organic compounds in serum by using gas chromatography coupled with triple quadrupole mass spectrometry]. / Determinazione di composti organoclorurati persistenti in siero mediante gascromatografia abbinata a spettrometria di massa con triple quadrupolo.

Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCs) are lipophilic and persistent compounds that were widely used in industrial and consumer products for decades until the late 70s. Due to their persistence and bioaccumulation, they are globally spread in the environment and may still be found in all environmental and biological media. Some have been classified as xenoestrogens or endocrine disruptors. Some others are known to have adverse effects for human health, including cancer. With the objective of establishing reference values, a fast and reliable method, previously developed and validated using single quadrupole mass spectrometry, was properly modified in order to simultaneously detect 10 organochlorine pesticides and 15 PCBs by using triple quadrupole. Use of triple quadrupole mass spectrometry has further increased the reliability of the method, so that it is now possible to collect more significant data concerning general population, which is the first step before the assessment of occupational exposure levels.

Apollon gene silencing induces apoptosis in breast cancer cells through p53 stabilisation and caspase-3 activation.

We analysed the effects of small interfering RNA (siRNA)-mediated silencing of Apollon, a member of the inhibitors of apoptosis protein family, on the proliferative potential and ability of human breast cancer cell lines to undergo apoptosis. In wild-type p53 ZR75.1 cells, Apollon knockdown resulted in a marked, time-dependent decline of cell growth and an increased rate of apoptosis, which was associated with p53 stabilisation and activation of the mitochondrial-dependent apoptotic pathway. Pre-incubation of cells with a p53-specific siRNA resulted in a partial rescue of cell growth inhibition, as well as in a marked reduction of the apoptotic response, indicating p53 as a major player in cell growth impairment consequent on Apollon silencing. Apollon knockdown induced consistently less pronounced anti-proliferative and pro-apoptotic effects in mutant p53 MDA-MB-231 cells than in ZR75.1 cells. Furthermore, the activation of caspase-3 seemed to be essential for the induction of apoptosis after Apollon knockdown, as the Apollon-specific siRNA had no effect on the viability of caspase-3-deficient, wild-type p53 MCF-7 cells or the ZR75.1 cells after RNA interference-mediated caspase-3 silencing. Our results indicate that p53 stabilisation and caspase-3 activation concur to determine the apoptotic response mediated by Apollon knockdown in breast cancer cells, and suggest Apollon to be a potential new therapeutic target for this malignancy.

Fallopian tube necrosis after postpartum sterilization.

Because it usually presents with nonspecific symptoms and occurs rarely, the diagnosis of fallopian tube torsion and necrosis is usually done at laparotomy. A 32 year-old woman returned to the hospital with right lower quadrant pain three days after a postpartum tubal sterilization procedure. Clinical, laboratory and imaging findings did not assist with the diagnosis. At laparotomy, after dissection of adhesions, a necrotic right fallopian tube was found. A salpingectomy was performed and the patient had an uneventful postoperative course. Fallopian tube torsion should be included in the differential diagnosis of pelvic pain in women. This patient has a good prognosis.

Nonsurgical management of genital prolapse. A review and recommendations for clinical practice.

The prevalence of genital prolapse increases with age. Because more women are living longer, genital prolapse will become even more common in our daily practices. Currently this complication is treated surgically, and there is minimal information about nonsurgical treatments. The National Library of Medicine was electronically searched for current information about the nonsurgical treatment of genital prolapse. This article summarizes the anatomic basis, the standard nomenclature, common symptoms and nonsurgical treatment of prolapse. Pessaries offer an alternative, even temporarily, to surgical therapy. Some women use a pessary on a long-term basis. There is no evidence in the literature that monthly follow-up improves outcome. Once fitted satisfactorily, women who wear pessaries need to be evaluated every three to six months.

Rupture of a cesarean-scarred uterus: a community hospital experience.

Concerns that a scarred uterus may rupture during labor have contributed to increased cesarean rates. A previous cesarean has become one of the most common indications for abdominal birth. More women must deliver vaginally after cesarean if we are to reduce cesarean rates. This study evaluates the effect of decreasing cesarean rates and increased vaginal birth after cesarean (VBAC) rates on the incidence of uterine rupture in a community hospital. We studied data for women who delivered at our obstetrical unit from 1988 through 1997. During 1994 our department adopted strategies to reduce cesarean rates. Data from women who delivered from 1988 through 1993 (period A, before the policy change) were compared with data for those who delivered from 1994 through 1997 (period B, after the policy change) and evaluated by chi-square analysis. p < 0.05 was considered significant. The total cesarean rate decreased from 24.3% (period A) to 17.9% (period B) (p < 0.0001), whereas the primary cesarean rate decreased from 14.9% to 10.3% (p < 0.0001), and the repeat rate decreased from 9.4% to 7.6% (p < 0.0001). The VBAC rate increased from 13.0 to 28.6 (p < 0.0001), whereas the incidence of uterine rupture did not change. During the study period, the cesarean rate decreased while the VBAC rate safely increased. The incidence of uterine rupture remained unchanged.

Effect of decreasing cesarean births on maternal age-, parity- and ethnicity-associated cesarean rates.

OBJECTIVE: To evaluate the effect of decreasing cesarean births on the rates associated with maternal age, parity and ethnicity. STUDY DESIGN: During 1991-1997, 14,689 women delivered at our community hospital, 2,945 by cesarean (20.0%). The clinical and demographic characteristics of these women and their newborns were studied. The data were divided according to maternal age, parity and ethnicity. As cesareans began to decrease in our service during 1994, the data were also divided into two groups: group 1 (1991-1993) and group 2 (1994-1997). chi 2 analysis was used to evaluate the differences between the proportions. A P value < .05 was considered significant. RESULTS: Maternal and perinatal outcomes and some demographic characteristics did not change, while cesarean rates decreased. As compared to group 1, cesarean birth rates decreased in group 2, from 22.5% to 17.9% (P < .0001). The decrease was significant in every maternal age-, parity- and ethnicity-related subgroup, except for women with parity > 4 (16.7% vs. 16.3%, P = .835) and those > or = 36 years old (31.6% vs. 30.9%, P = .798); for them, cesarean birth rate for breech presentation increased in group 2 (1.3-4.7%, P = .002). CONCLUSION: Cesarean birth rates can be reduced safely, and further studies should determine the factors associated with higher cesarean rates among older women.

Vanishing forceps delivery.

This study evaluates the effect of decreasing cesarean rates and increasing regional anesthesia use on the frequency of forceps deliveries. Data of women who delivered at our community hospital from 1990 through 1997 are reviewed. In 1994, the members of our department adopted several strategies to decrease cesarean deliveries. The cesarean rate decreased whereas regional analgesia use increased. We studied the frequency and type of vaginal operative deliveries during this 8 year period. These data were evaluated by chi2 analysis. Data of women who delivered in the first 4 years (group 1) were compared with data of those who delivered in the second 4 years (group 2). A p < 0.05 was considered significant. The demographic and clinical characteristics of these women remained unchanged during the study period. The total cesarean rate decreased from 23.2% in group 1 to 17.9% in group 2 (p < 0.0001). The proportion of women who received regional anesthesia increased from 18.8 in group 1 to 25.7 in group 2 (p < 0.0001). Vaginal operative deliveries increased from 3.6 to 5.5 (p < 0.0001), whereas the proportion of forceps deliveries decreased from 2.2 to 1.5 (p = 0.001). Perinatal morbidity and mortality did not change. The decrease in cesarean rate and increase in regional anesthesia use were associated with an increase in operative deliveries; however, forceps deliveries continue to decrease in our community hospital.

Effect of prenatal care on infant mortality rates according to birth-death certificate files.

Infant mortality has decreased nationwide; however, our national rates still log behind those of other industrialized countries, especially the rates for minority groups. This study evaluates the effect of prenatal care and risk factors on infant mortality rates in Chicago. Using linked infant birth and death certificates of Chicago residents for 1989-1995, a total of 5838 deaths occurring during the first year of life were identified. Birth certificate variables, especially prenatal care, were reviewed. Variables were compared by stratified analysis. Pearson chi 2 analysis and odd ratios (ORs) were computed. Infant mortality rate (IMR) in Chicago decreased from 17 in 1989 to 12.6 in 1995 (P < .0001). Some factors increased IMR several fold: prematurity (OR 17.43), no prenatal care (OR 4.07), inadequate weight gain (OR 2.95), African-American ethnicity (OR 2.55), and inadequate prenatal care (OR 2.03). Compared with no care, prenatal care was associated with lower IMR; however, early care was associated with higher IMR and ORs than later care. These results demonstrate prenatal care is associated with lower IMR; however, compared with late prenatal care, early care does not improve IMR. Further studies should evaluate whether improving the quality of care improves IMRs.

Cervical ripening. A review and recommendations for clinical practice.

Cervical ripening occurs before the onset of labor. The cervix is metabolically active during ripening and passive during active labor. A ripe cervix indicates readiness for labor and predicts successful induction of labor. Practitioners evaluate cervical readiness for labor using the Bishop score. Membrane stripping, mechanical dilators and prostaglandins are ripening methods used frequently because they are simple, effective, efficient, safe and well tolerated. Stripping of membranes, a Foley catheter and misoprostol tablets are less expensive than other available methods. Because prostaglandins may cause excessive myometrial activity and even labor, hospitalization and fetal monitoring are recommended. Despite their effectiveness, these methods often do not decrease the cesarean section rates. This finding may be explained by the fact that each study reviewed only included a small number of patients and that in most cases, amniotomy was done and induction started, when feasible, before the women reached a Bishop score > or = 9. Larger studies may have different outcomes. The type of ripening methods used depends on the urgency of the situation; balloon catheters and prostglandins often act within 12 hours, while membrane stripping is less predictable.

Correlation of birth weights with cesarean rates.

OBJECTIVE: To determine whether birth weights correlate with cesarean indications and whether a decrease in cesarean rates affects this relationship. MATERIALS AND METHODS: During the 1991-1997 period, 14 689 women delivered at Ravenswood Hospital Medical Center, Chicago; 2945 by cesarean (20.0%). We studied birth weight groups (Group 1, < or = 2500 g; Group 2, 2501-4000 g; and Group 3, > 4000 g) according to the indication for cesarean delivery. Group 3 was divided into two subgroups (3a: 4001-4500 g, and 3b: > 4500 g). As cesarean rates decreased in our unit after 1994, we separated the data into two periods: A (1991-1993) and B (1994-1997). The differences between proportions were analyzed using the chi2 tables. A P < 0.05 value was considered significant. RESULTS: Two out of 10 women admitted to our unit were delivered by cesarean. Compared to Group 2 (average weight), rates for breech and 'other' indications were higher in Groups 1 and 3 (P < 0.001); the repeat cesarean rate was the lowest in Group 1. Rates for dystocia increased with birth weight. In Group 3, one out of four newborns (one out of three newborns > 4500 g in Subgroup 3b) had a cesarean birth, more than half of them for indications other than dystocia. Compared to Period A, Period B shows lower cesarean rates in Group 2 (21.4 vs. 16.4, P < 0.0001) and Subgroup 3b (35.4 vs. 26.1, P = 0.041). CONCLUSIONS: Birth weights affect cesarean delivery rates. Small and large newborns have more cesarean deliveries than those of average weight, whereas cesarean for dystocia increases with birth weights. Cesarean rates for non-reassuring fetal status are similar in all groups. A decline in repeat and cesareans for dystocia determined the lower total cesarean rate during the second period. and snhtetricrr

Effects of obstetrician characteristics on cesarean delivery rates. A community hospital experience.

OBJECTIVE: Despite a decrease in the overall cesarean delivery rate at Ravenswood Hospital Medical Center in Chicago, a wide range of variation existed among individual obstetricians' rates. This study evaluated obstetricians' characteristics to determine whether they affected cesarean delivery rates. STUDY DESIGN: In 1994 members of my department adopted strategies to decrease the cesarean delivery rate. Data on women who were delivered at the obstetric unit from 1994-1997 and data on their neonates were studied. Certain characteristics of obstetricians were also analyzed. The data were grouped according to personal characteristics and obstetricians' cesarean delivery rates: group 1 had a low rate (15%). Pearson chi2 analysis was used to evaluate the differences between the proportions. P <.05 was considered significant. RESULTS: The departmental cesarean delivery rate decreased from 20.5% in 1994 to 15.5% in 1997 (P <.0001), whereas individual obstetricians' rates varied from 0% to 44.4%. Obstetricians in group 1 (average rate 12.2%) and group 2 (average rate 20.8%, P <.0001) served similar populations with similar outcomes. Compared with obstetricians in group 2, those in group 1 (low rate) performed more vaginal deliveries after cesarean birth and used epidural analgesia and the vacuum extractor more frequently. Young age of physician, graduation from a domestic medical school, group practice, and smaller volume of births were all significantly linked to lower cesarean delivery rates. CONCLUSIONS: Cesarean delivery rates can safely be reduced. Certain individual obstetrician characteristics influence cesarean delivery rates. Obstetricians' commitment facilitates lowering of cesarean delivery rates.

Influence of maternal ethnicity on infant mortality in Chicago, 1989-1996.

This study compared infant mortality rates between large ethnic groups in Chicago from 1989-1996. Infant mortality information about ethnic groups was compared using data from annual reports published by the Epidemiology Program, Department of Public Health, City of Chicago and vital statistics documents in Illinois, which include information on ethnicity. Chi-squared analysis was used to evaluate the differences between the proportions. A P value of < .05 was considered significant. During the study period, there were 461,974 births and 6407 infant deaths in Chicago. African Americans contributed 212,924 (46.1%) births and 4387 (68.5%) deaths; Hispanics 132,787 (28.7%) births and 1166 (18.2%) deaths; and whites 99,532 (21.6%) births and 780 (12.2%) infant deaths. Compared with the other groups. African Americans suffered a twofold increased mortality (P < .00001) for five of the six most common causes of infant mortality. Deaths from congenital malformations, although significant, were not excessively increased among African Americans (P = .014). Hispanics demonstrated a higher mortality rate than whites (P = .01), especially for postnatal mortality and respiratory distress syndrome. These data confirm excessive infant mortality among African Americans. Further studies are needed to evaluate the apparent low mortality among some Hispanics compared with the other groups studied.

Effect of departmental policies on cesarean delivery rates: a community hospital experience.

OBJECTIVE: During 1994, our department adopted several strategies in an attempt to decrease our cesarean delivery rates. This study evaluates the effect of these changes on our cesarean delivery rates. METHODS: We studied data of women who delivered at our community hospital obstetric unit over a period of 6 years, from January 1, 1991, to December 31, 1996. During 1994, our department adopted labor management and cesarean delivery guidelines, with review of every cesarean delivery that did not meet guidelines and confidential individual feedback; established 24-hour in-house coverage; and attempted to achieve the goal of an annual cesarean delivery rate of less than 15%. These data were evaluated by chi2 analysis. Women who delivered in the first 3 years (group A) were compared with those who delivered in the second 3 years (group B) (ie, when the changes occurred). P < .05 was considered significant. RESULTS: Groups A and B shared similar demographic characteristics. The total cesarean delivery rate decreased from 22.5% (group A) to 18.6% (group B) (P = .001), whereas the primary cesarean delivery rate decreased from 13.5% to 10.6% (P = .001) and the repeat cesarean delivery rate decreased from 9.0% to 7.9% (P = .03). The proportion of women who received oxytocin and regional anesthesia and underwent vacuum-assisted deliveries increased (P < .001), whereas perinatal mortality and morbidity did not change. CONCLUSION: The cesarean delivery rate safely decreased. These data suggest the importance of the commitment of attending physicians to a lower cesarean delivery rate, of service improvements, and of detailed feedback.

Hemoperitoneum in a postmenopausal woman.

As the number of postmenopausal women increases, physicians will have more opportunities to treat elderly women with gynecological complications. This case report describes a 76-year-old, obese, multiparous woman, known to have gallstones who presented with acute abdomen complaints and was admitted for observation. Treatment was delayed until significant blood loss was recognized. At laparotomy, a ruptured ovarian granulosa cell tumor was found.

Bilateral hip dysplasia. A case report.

BACKGROUND: Hip dysplasia affects 1% of newborns. Our health system screening begins at birth, and our educational system requires health screens at various ages, so physicians in this country rarely find an adult with an undiagnosed congenital condition. CASE: Bilateral hip dislocation was diagnosed on a 20-year-old, nulliparous woman who had just arrived from Puerto Rico. She tolerated her abnormal gait well, unaware of the condition of her hips. After an unremarkable prenatal course, she was admitted at term with ruptured membranes for stimulation of labor. She developed secondary arrest of labor, and a healthy, 3,180-g, female infant was delivered by cesarean. CONCLUSION: In hip dysplasia, early diagnosis (and therapy) prevents long-term consequences.

Premature rupture of membranes.

The management of patients with premature rupture of membranes has changed markedly in the past several years. The basis for this is a combination of a better understanding of newborn physiology, improved neonatal care, refinements in antibiotic therapy, and the widespread use of maternal and fetal monitoring. The best outcome for both mother and infant undoubtedly reflects data based on a combination of factors, among which are gestational age survival, evidence of fetal distress, presence or absence of labor and sepsis, and of course, the cervical condition as it is related to labor-readiness. An important recent advance is the recognition that an active observation management program is associated with less morbidity and mortality than the classic management course of delivery within 12 hours of membrane rupture. The fact that preterm premature rupture of membranes tends to recur in subsequent pregnancies offers an opportunity for prevention. Moreover, advances in perinatal and neonatal care will continue to improve the outcomes of these women and their children.