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Michael G Ross

Publications and source records attributed to Michael G Ross.

At least 19 recordsLinked to original sources
PubMed2006

A mathematical model of twin-twin transfusion syndrome with pulsatile arterial circulations.

The twin-twin transfusion syndrome (TTTS) is a severe complication of monochorionic twin pregnancies caused by a net transfusion of blood from one twin (the donor) to the other (the recipient) through placental anastomoses. To examine the pathophysiology of TTTS evolving through clinical stages I to IV, we extended our mathematical model to include pulsating circulations propagating along the arterial tree as well as placental and cerebral vascular resistances, and arterial wall thickness and stiffness. The model demonstrates that abnormal umbilical arterial flow (TTTS stage III) in the donor twin results from increased placental resistance as well as reduced resistance in the cerebral arteries. In contrast, recipient twin abnormal umbilical arterial flow requires a significantly greater increase in placental resistance, resulting from the compressive effects of high amniotic fluid pressure. Thus simulated abnormalities of donor umbilical arterial pulsations occur in the donor more commonly and earlier than in the recipient. The "normal" staging sequence (I, II, III, IV) correlates with the presence of compensating placental anastomoses, constituting the majority of monochorionic twin placentas. However, TTTS stage III may occur before manifestations of stage II (lack of donor bladder filling), in our model correlating with severe TTTS from a single arteriovenous anastomosis, an infrequent occurring placental angioarchitecture. In conclusion, this mathematical model describes the onset and development of the four stages of TTTS, reproduces a variety of clinical manifestations, and may contribute to identifying the underlying pathophysiology of the staging sequence in TTTS.

Chorion↗
PubMed2006

Gender-specific orexigenic and anorexigenic mechanisms in rats.

Feeding dysregulation may manifest as either under-nourishment (e.g., anorexia) or excessive eating leading to obesity. Recent studies have suggested a gender-related variance in weight maintenance in response to chronic disease or obesity-related dietary regimens. However it is unclear whether these gender differences in weight management are secondary to appetite-mediated food intake or alternative mechanisms (e.g., exercise, metabolism). In this study, we explored gender-dependent feeding and hormonal responses to dietary restriction (12-h fast) or to an inflammatory stimulus (LPS, 100 microg/kg b.w.; i.p.) in rats. In response to a 12 h fast, female rats increased (p<0.05) total daily food intake above that of male rats by primarily increasing nighttime feeding by 40%, as compared to 10% in males. Consistent with the increased food intake, fasting induced a greater percent increase in female as compared to male plasma ghrelin (141 vs. 65%, p<0.001). In response to LPS, both male and female rats showed similar reductions in total daily food consumption. However LPS (6 h) induced a greater percent increase in plasma leptin in female than male rats (230 vs. 33%, p<0.01), whereas ghrelin was similarly decreased in both females and males (66 vs. 44%). These findings demonstrate sexual dimorphic responses in feeding and appetite-associated hormonal responses to fasting or LPS treatment. Our findings suggest that therapeutic interventions with ghrelin or leptin must be modified according to gender in order to optimally achieve either weight loss for obesity or weight gain/maintenance for chronic illness-associated anorexia.

Animals↗
PubMed2006

N-acetyl-cysteine suppresses amniotic fluid and placenta inflammatory cytokine responses to lipopolysaccharide in rats.

OBJECTIVE: Maternal infections may induce placental, amniotic and, potentially, fetal inflammatory responses. As cytokine responses may be mediated by oxidative stress, we determined whether the antioxidant N-acetyl-cysteine (NAC), can attenuate maternally induced amniotic and placental cytokine responses to maternal infection (modeled by lipopolysaccharide [LPS]). STUDY DESIGN: Gestation day 18 pregnant rats were (1) treated with LPS (100 microg/kg, body weight; intraperitoneally) alone; (2) pretreated with NAC (300 mg/kg body weight; intraperitoneally) 30 minutes before LPS; (3) posttreated with NAC 120 minutes after LPS; or (4) treated with NAC 30 minutes before and 120 minutes after LPS. Six hours after LPS administration, maternal serum and amniotic fluid interleukin-6 (IL-6) and IL-10 levels, and placental IL-6 messenger RNA levels were determined. RESULTS: LPS increased maternal serum IL-6 (50 +/- 25 to 3444 +/- 584 pg/mL) and IL-10 (40 +/- 20 to 958 +/- 339 pg/mL) and amniotic fluid IL-6 (59 +/- 25 to 891 +/- 128 pg/mL). Pretreatment and/or posttreatment with NAC attenuated IL-6 in the maternal serum and amniotic fluid and IL-10 in the amniotic fluid. LPS also induced placental IL-6 messenger RNA that was inhibited by treatment with NAC before and after LPS. CONCLUSION: NAC inhibition of inflammatory responses may protect the fetus from potential long-term sequelae.

Acetylcysteine↗
PubMed2006

Maternal N-acetylcysteine suppresses fetal inflammatory cytokine responses to maternal lipopolysaccharide.

OBJECTIVE: Evidence suggests that maternal infections may induce fetal inflammatory responses. Because cytokine actions may be mediated by oxidative stress, we determined whether N-acetylcysteine, an antioxidant, can blunt fetal inflammatory responses to maternal lipopolysaccharide. STUDY DESIGN: Sprague Dawley near-term rats (n = 16) received intraperitoneal lipopolysaccharide (100 microg/kg) at 30 minutes and saline solution or N-acetylcysteine (300 mg/kg) at 150 minutes. An additional group received N-acetylcysteine before and after lipopolysaccharide administration. At 6 hours, rats were killed, and fetal and maternal blood cytokines were determined. RESULTS: After maternal lipopolysaccharide administration, fetal blood interleukin-6 markedly increased (3 +/- 2 to 1265 +/- 574 pg/mL); N-acetylcysteine that was given before or before and after lipopolysaccharide administration reduced fetal interleukin-6 response to control levels. A similar trend was observed for interleukin-1beta. No effect of N-acetylcysteine on fetal interleukin-10 levels was observed. CONCLUSION: Maternal N-acetylcysteine inhibits fetal cytokine responses to maternal lipopolysaccharide, even when given 2 hours after lipopolysaccharide injection. These results suggest that N-acetylcysteine may protect the fetus from sequelae of maternal inflammation.

Acetylcysteine↗
PubMed2006

Aquaporin 3 expression in human fetal membranes and its up-regulation by cyclic adenosine monophosphate in amnion epithelial cell culture.

OBJECTIVE: The cell membrane water channel protein aquaporins (AQPs) may be important in regulating the intramembranous (IM) pathway of amniotic fluid (AF) resorption. The objective of the present study was to determine whether aquaporin 3 (AQP3) is expressed in human fetal membranes and to further determine if AQP3 expression in primary human amnion cell culture is regulated by second-messenger cyclic adenosine monophosphate (cAMP). METHODS: AQP3 expression in human fetal membranes of normal term pregnancy was studied by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC). To determine the effect of cAMP on AQP3 expression, primary human amnion cell cultures were treated in either heat-inactivated medium alone (control), or heat-inactivated medium containing: (1) SP-cAMP, a membrane-permeable and phosphodiesterase resistant cAMP agonist, or (2) forskolin, an adenylate cyclase stimulator. Total RNA was isolated and multiplex real-time RT-PCR employed for relative quantitation of AQP3 expression. RESULTS: We detected AQP3 expression in placenta, chorion, and amnion using RT-PCR. Using IHC, we identified AQP3 protein expression in placenta syncytiotrophoblasts and cytotrophoblasts, chorion cytotrophoblasts, and amnion epithelia. In primary amnion epithelial cell culture, AQP3 mRNA significantly increased at 2 hours following forskolin or SP-cAMP, remained elevated at 10 hours following forskolin, and returned to baseline levels by 20 hours following treatment. CONCLUSION: This study provides evidence of AQP3 expression in human fetal membranes and demonstrates that AQP3 expression in primary human amnion cell culture is up-regulated by second-messenger cAMP. As AQP3 is permeable to water, urea, and glycerol, modulation of its expression in fetal membranes may contribute to AF homeostasis.

Amnion↗
PubMed2006

Gestational programming of offspring obesity/hypertension.

The intrauterine milieu impacts fetal growth directly during gestation. It is now clear, however, that postnatal phenotype is also influenced by prenatal conditions. A variety of disorders in the adult have been linked to fetal size at birth; these include glucose intolerance, cardiovascular disease, and the subjects of this review, obesity and hypertension. We will review recent data regarding these associations and the pathophysiologic mechanisms underlying them in humans as well as in animal models.

Animals↗
PubMed2006

Cervical neck dislocation associated with the Zavanelli maneuver.

BACKGROUND: In the management of shoulder dystocia, fetal head replacement into the uterus has been advocated should delivery attempts remain unsuccessful. Reports of the Zavanelli maneuver have been remarkably optimistic despite the challenges of the procedure. CASE: A gravida 3 para 2 (two previous vaginal deliveries of more than 4,500-g infants) with gestational diabetes presented at term. Following a low forceps delivery, shoulder dystocia was encountered and was unable to be relieved with standard maneuvers. A cesarean delivery was performed, shoulders disimpacted, and the infant delivered abdominally. A 4,680-g stillborn infant was delivered with radiologic and autopsy evidence of cervical C5-C6 dislocation. CONCLUSION: Despite published reports of high success rates and limited fetal consequences, physicians should be aware of adverse consequences including cervical neck trauma associated with use of the Zavanelli maneuver.

Adult↗
PubMed2005

Protective effect of prenatal water restriction on offspring cardiovascular homeostasis in response to hemorrhage.

We determined the cardiovascular and AVP responses of prenatally dehydrated (PreDehy) neonates to intravascular hemorrhage. Ewes with singleton fetuses were subjected to water restriction from 110 days of gestation to full term to achieve hypernatremia of 8-10 meq/l. Water and food were provided ad libitum to control ewes. After delivery, water and food were provided ad libitum to ewes from both groups, and newborns were allowed to nurse ad libitum. At 15 +/- 2 days of age, PreDehy and control lambs were prepared with bladder and femoral catheters and studied at 25 +/- 2 days of age. After a 2-h basal period, lambs were hemorrhaged to 30% of blood volume over 1 h (0.5% of blood volume/min) and monitored 1 h after hemorrhage. Neonatal arterial blood pressure was measured, and blood samples were collected. Basal plasma sodium levels, plasma osmolality, hematocrit, and mean arterial pressure were increased in PreDehy lambs compared with controls. Both groups had similar basal AVP levels and heart rate. In response to hemorrhage, all parameters remained significantly elevated in PreDehy lambs. Blood pressure decreased less in PreDehy lambs than in controls. The hemorrhage-AVP threshold (percent blood volume withdrawal at which plasma AVP values significantly increased) was markedly elevated (20 vs. 15%) and peak hemorrhage-induced AVP plasma levels were lower (5.6 +/- 1.5 vs. 10.1 +/- 1.5 pg/ml, P < 0.01) in PreDehy lambs than in controls. Thus offspring of dehydrated ewes demonstrate enhanced AVP secretory responses to hypotension. Despite potential long-term adverse effects of systemic hypertension, these results suggest a protective effect of prenatal water restriction on offspring cardiovascular homeostasis during blood volume reduction.

Animals↗
PubMed2005

Programmed syndrome of hypernatremic hypertension in ovine twin lambs.

OBJECTIVE: An increased risk of adult hypertension, obesity, and coronary heart disease occurs in low birth weight or intrauterine growth-restricted newborn infants as a result of fetal programming. Human twins represent a natural model of low birth weight and intrauterine growth restriction because they are significantly smaller at birth than singleton infants because of both earlier delivery and reduced intrauterine growth. Increased blood pressure has been reported in several epidemiologic studies of human twin offspring, although this has not been confirmed in an animal model. Because the sheep pregnancy consists of singleton and twin litters, we sought to determine the impact of ovine twin gestation and twin nursing on the cardiovascular and renal function of the offspring. STUDY DESIGN: Newborn lambs (n = 12) were studied at 21 +/- 2 day of life. Both singleton (n = 6) and twin lambs (n = 6) were born to ewes provided ad libitum water and food throughout gestation. After the delivery, ewes were provided ad libitum water and food, and newborn lambs were allowed ad libitum nursing with the maternal ewe. At 15 +/- 2 days of age, the lambs were prepared with vascular and renal catheters and studied at 21 +/- 2 days. After a 2-hour basal period, lambs received an intravenous infusion of hypotonic (0.075 mol/L) NaCl (0.15 ml/kg/hr) for an additional 2 hours. Newborn arterial blood pressure, heart rate, and urine flow were monitored continuously, and arterial blood samples were obtained before, during, and after the infusion. RESULTS: At birth, twin lambs weighed 30% less than singleton lambs (3.5 +/- 0.1 kg vs 5.0 +/- 0.2 kg; P < .05), although 50% less at 21 days (5.2 +/- 0.6 vs 10.8 +/- 1.2 kg). There were marked differences in basal arterial blood values between twin and singleton lambs at 21 days, with twins having significantly increased plasma sodium and systolic, diastolic, and mean arterial pressures and reduced glomerular filtration rates, urine osmolality, osmolar excretion, and osmolar clearance (per kg body weight) compared with singleton lambs. In response to hypotonic saline solution infusion, the plasma composition and blood pressure differences between twin and singleton lambs persisted. CONCLUSION: These results indicate that ovine twin gestation and nursing markedly reduced body weight at 21 days of age, with evidence of plasma hypernatremia, hypertension, and reduced glomerular filtration rates, which persisted throughout hypotonic saline solution infusion. Consistent with epidemiologic studies of humans, these results demonstrate that gestational/newborn nutrient stress may program hypertension in offspring.

Animals↗
PubMed2005

Cloning and cellular expression of aquaporin 9 in ovine fetal membranes.

OBJECTIVE: Amniotic fluid (AF) absorption across fetal membranes is essential for AF volume homeostasis, balancing fetal swallowing, urine flow, and lung liquid production. In sheep, AF is absorbed primarily across the amniotic membrane into fetal vasculature situated between the amnion and chorion. Aquaporins (AQPs) are cell membrane proteins that serve as water channels. Recent studies have demonstrated the expression of AQP 1, 3, 8, and 9 in human chorioamniotic membranes and placenta. As AF dynamics continued to be explored primarily in the ovine model, we sought to clone and characterize the expression of ovine AQP9 in fetal membranes. METHODS: Ovine AQP9 gene was cloned with the use of homology reverse transcriptase-polymerase chain reaction (RT-PCR). RT-PCR and Northern analysis were used to determine AQP9 gene expression, and immunohistochemistry (IHC) used to localize AQP9 protein expression in ovine fetal membranes. RESULTS: A 2085-base pair (bp) full-length complementary DNA (cDNA) sequence of ovine AQP9 was cloned. The ovine AQP9 cDNA is 86%, 82%, and 82%, and the predicted amino acid sequence (295 amino acids) is 77%, 71%, and 69% identical to human, rat, and mouse AQP9, respectively. RT-PCR and Northern analysis detected AQP9 messenger RNA expression in ovine amnion and allantois, but not in placenta, chorion, or umbilical cord. Immunohistochemistry localized AQP9 protein in epithelia of amnion and allantois. CONCLUSION: The presence of significant AQP9 messenger RNA and protein expression in ovine fetal membranes suggests that AQP9 may be a major water channel for intramembranous AF resorption in sheep. The cloning of ovine AQP9 and the demonstration of AQP9 expression in amnion and allantois significantly enhances our understanding of ovine AF regulation and offers the potential for therapeutic approaches for the treatment of oligohydramnios and polyhydramnios.

Allantois↗
PubMed2005

Simulation of therapy in a model of a nonhydropic and hydropic recipient in twin-twin transfusion syndrome.

OBJECTIVE: This study was undertaken to model the sequence of events that occurs after amnioreduction, laser therapy, and digoxin administration in twin-twin transfusion syndrome (TTTS) with and without a hydropic recipient twin. STUDY DESIGN: We added amnioreduction, laser therapy, and digoxin administration to our mathematical TTTS model and simulated combinations of these therapies. RESULTS: With a nonhydropic recipient, simulated amnioreduction delays the onset of hydrops. Conversely, with a hydropic recipient, amnioreduction aggravates the degree of hydrops. Furthermore, amnioreduction increases the transplacental fluid flow and may temporarily cause a hydropic donor. Laser therapy terminates the cause of recipient hydrops. Digoxin reduces the degree of recipient hydrops, but increases arteriovenous fetofetal transfusion. CONCLUSION: Laser therapy is superior in TTTS with a hydropic recipient, because simulated amnioreduction aggravates the recipient's cardiovascular status. Digoxin benefits a hydropic recipient but slightly worsens the donor's condition. Therefore, TTTS presenting with a hydropic recipient prior to fetal viability (approximately 26 weeks) may be best treated with laser therapy, whereas more advanced gestations may be offered digoxin administration plus amnioreduction, to delay the progression of TTTS.

Cardiotonic Agents↗