Placenta Of Animals Research Articles

Seroprevalence and risk factor analysis of brucellosis among dairy farmers in Aligarh region, North India: creating awareness of a neglected disease.

Introduction. Brucellosis, a globally distributed zoonotic disease, is caused by the Gram-negative bacteria known as Brucella. Humans acquire infection through direct contact with the blood, urine and placenta of animals, inhalation of dust or aerosols at infected animal farms, and raw milk and meat intake. This study aimed to assess the prevalence of brucellosis in dairy farmers in and around the Aligarh region of North India, to document various clinical signs and symptoms in Brucella-positive individuals, and to create awareness in dairy farmers concerning brucellosis and ways to prevent it. Methods. This was an observational study that included 125 dairy farmers in and around the Aligarh region. Serum samples were taken from this high-risk group after obtaining informed consent. Further, a pre-designed proforma was used to collect information about their knowledge, attitude and practices (KAP) concerning brucellosis and assess the risk factors for the disease. The Rose Bengal test (RBT), serum agglutination test (SAT) and enzyme-linked immunosorbent assay (ELISA) were performed to detect the seroprevalence of brucellosis. Result.Brucella infection was diagnosed in 64 (51.20 %) cases by indirect ELISA (IgM+IgG), 41 (32.8 %) by RBT and 4 (3.2 %) by SAT. Significant clustering of patients was seen in the 20-55 years age group. The most common symptoms in ELISA IgM-positive patients were joint pain (16.07 %), fatigue (14.28 %), anorexia (12.50 %), weight loss (8.92 %), malaise (5.35 %), undulant fever (3.57 %), night sweats (3.57 %) and headache (1.78 %). The findings of this study indicate that ELISA (IgM+IgG) exhibits great sensitivity as compared to SAT and RBT. KAP was very poor among dairy farmers. Conclusion. In India, Brucella is a frequent but severely underreported illness. ELISA is the most sensitive serological test for diagnosing brucellosis. No potential vaccine has yet been introduced for humans against brucellosis. Thus, it is necessary to impart awareness and sensitize high-risk groups concerning brucellosis.

Disruption of the Expression of the Placental Clock and Melatonin Genes in Preeclampsia.

Circadian rhythms have been described in numerous tissues of living organisms and are necessary for homeostasis. The understanding of their role in normal and pathological pregnancy is only just emerging. It has been established that clock genes are expressed in the placenta of animals and humans, but the rhythmicity of placenta immune cells is not known. Macrophages from healthy placenta of women at term were isolated and the expression of clock genes BMAL1, CLOCK, PER2, CRY2, and NR1D1 was assessed by qRT-PCR every 4 h over 24 h. Raw data were treated with cosinor analysis to evaluate the significance of the oscillations. Placental macrophages exhibited significant circadian expression of clock genes but one third of placental macrophages lost clock gene rhythmicity; the clock gene oscillations were restored by co-culture with trophoblasts. We wondered if melatonin, a key hormone regulating circadian rhythm, was involved in the oscillations of placental cells. We showed that macrophages and trophoblasts produced melatonin and expressed MT2 receptor. In women who developed preeclampsia during pregnancy, circadian oscillations of placental macrophages were lost and could not be rescued by coculture with trophoblasts from healthy women. Moreover, production and oscillations of melatonin were altered in preeclamptic macrophages. For the first time to our knowledge, this study shows circadian rhythms and melatonin production by placental macrophages. It also shows that preeclampsia is associated with a disruption of the circadian rhythm of placental cells. These results represent a new scientific breakthrough that may contribute to the prevention and treatment of obstetrical pathologies.

Expression dynamics of Crry at the implantation sites in normal pregnancy and response against miscarriage induction.

In mammals, immune tolerance against fetal tissue has been established for normal pregnancy progression. It is known that Crry regulates complemental activity to prevent injury of the mouse embryo and extra-embryonic tissue. This study aimed to examine the expression appearance and normal localization sites of Crry in the mouse placenta. Also, the emergency responses of Crry were verified at the time of experimental miscarriage induction. Moreover, we investigated an existing similar protein of Crry in animal placentas other than mice. Crry expression level showed a peak at day 8.5 of pregnancy. Trophoblast giant cells and decidual cells indicated a positive reaction to anti-Crry antibody. After treatments of interferon-γ, Crry expression was increased significantly in the survived implantation sites as compared with the controls. However, there was no significant difference in the miscarriage-initiated sites. It disclosed that Crry distributes from the early to middle periods of the placentas and involves complement regulation at the extraembryonic tissue and decidua basalis. Crry also showed an ability to respond to risk against external initiation for urgent miscarriage. Finally, we found anti-mouse Crry antibody-bound proteins in the placenta of many animals. It suggests a potency of Crry to make an environment of immune tolerance in many types of mammal placentas.

Seroprevalence of Brucella infection and associated factors among pregnant women receiving antenatal care around human, wildlife and livestock interface in Ngorongoro ecosystem, Northern Tanzania. A cross-sectional study

BackgroundBrucellosis is a zoonotic disease transmitted to humans through contact with infected animals, animal products or consumption of infected dairy products. Brucella infection during pregnancy is of special interest due to association with adverse pregnancy outcomes. This study determined the seroprevalence and factors associated with Brucella infection among pregnant women around the human-wildlife-livestock interface area in Ngorongoro ecosystem, Northern Tanzania.MethodsA facility-based cross-sectional study was conducted between May and June 2018 at six health facilities that provide antenatal services. Pregnant women receiving antenatal care were invited to participate. A structured questionnaire was used to collect socio-demographic and obstetric characteristics in addition to behavior and practices related to the occurrence of human brucellosis. The presence of serum immunoglobulin against Brucella was determined using Rose Bengal Plate Test (RBPT). The positive samples were further assayed for the presence of IgG and IgM using The enzyme-linkedimmunosorbent assay. Bivariate analysis was conducted to determine the variables associated with Brucella seropositivity. Multivariable logistic regression analysis was performed to examine the factors independently associations with Brucella seropositivity after adjustment for other explanatory variables.ResultsA total of 313 participants were enrolled in the study. The overall seroprevalence of Brucella infection was 10.9% (34/313) determined by Rose Bengal plate test. Of 34 positive individuals, 27(79.4%) and 8(23.5%) were positive in the ELISA specific for IgG and IgM Brucella antibodies respectively. Regular contact with manure (AOR 3.16, 95%CI 1.27–7.83) and preference for animal fresh milk (AOR 3.80, 95% CI 1.23–11.69), raw meat (AOR 2.58, 95% CI 1.14–5.81) and raw animal blood (AOR 2.71, 95% CI 1.15–6.35) increased the odds of being Brucella seropositive. Contact with the animal placenta were not associated with Brucella seropositivity after adjustment.ConclusionThis study has found that brucellosis is an important public health problem among pregnant women in areas with interactions of humans; livestock and wildlife. The risk of infection increased with the regular contact with manure and preference of raw foodstuffs like animal blood, meat, and milk. We emphasize the need for interventional strategies to reduce the risk of exposure.

Histopathological findings and immunohistochemical staining of Neospora caninum infection in placentas of animals for slaughter

Bovine neosporosis is a parasitic disease caused by the protozoan Neospora caninum, which is one of the main pathogens that cause abortions in cattle worldwide. It is responsible for large losses in dairy and beef cattle, especially with regard to the expenses associated with decreased productivity and increased discard. In the State of Maranhão, the occurrence of this parasite has already been confirmed in the dairy cattle of three microregions that make up the state’s dairy industry and in small ruminants of the municipalities of Amarante do Maranhão and Buritirana. This fact justifies the importance of determining the presence of N. caninum in cattle slaughtered in the slaughterhouses of the Island of São Luís, to help control the parasitic cycle in the cattle production system of the region under study, and the importance of its diagnosis. The objective of the research was to conduct a histopathological and immunohistochemical characterization of bovine placentas infected with N. caninum collected in slaughterhouses. Sixteen placenta samples from cows were randomly selected at the slaughterhouses of the city of São Luís for histological analysis and immunohistochemistry. Results showed that 31% of the placentas presented histopathological changes such as: inflammatory process, edema, hemorrhage and presence of hemosiderin. All slides with histopathological changes showed immunolabeling for N. caninum.

Self-Reported Selected Zoonotic Diseases among Animal Handlers in Ahmedabad City

ObjectiveThe present study aims to document the burden of self-reported selected zoonotic diseases (Z/D/S) among animal handlers in urban areas of AhmedabadIntroductionThe usual mechanism of disease or infection transmission from vertebrate animals to humans and vice-versa is classified as zoonosis [1]. Globally out of all microbial pathogenic disease, 61% are zoonotic with 13% species are regarded as emerging or reemerging [2]. Studies suggest the prevalence of innumerable known and important Z/D/S such as leptospirosis, rabies, avian influenza but the extent of burden of zoonotic diseases amongst high-risk cohorts such as animal handlers within urban geography not adequately documentedMethodsA cross-sectional study conducted amongst animal handlers residing in the urban/peri-urban areas of Ahmedabad. A purposive sample of 170 animal handlers was included in this study. The sample size estimated based on operational feasibility and response saturation for 10%. All individuals engaged in handling animals (such as cattle, buffalos, cows, goat, dog, hen, sheep etc.) recruited from three different zones (South, East, and New west zone) randomly out of six zones of Ahmedabad city, Gujarat, India. Data collected in vernacular language by using pretested questionnaire during the month of March to May 2017. Data entered into Excel and analyzed by using SPSS V.18. The burden was estimated in form of proportion of self-reported disease. The ethical permission was sought from the ethical review board of Indian Institute of Public Health GandhinagarResultsTotal 170 animal handlers participated in this study and majority of them were females. Around 76% participants belonged to 26 to 60 years of age group with the mean age of 42±15years. There were 44% of respondents illiterate however out of total literate, 50% studied up to primary or more. Around one-third, respondents belonged to Below Poverty Line status.The cumulative prevalence of self-reported Z/D/S was found 23% among respondents however amongst their family members was found 17%. The point prevalence of self-reported Z/D/S during the study was found to be 17% and 18% amongst their family members. Self-reported Z/D/S includes vector born, animal bite and respiratory diseases.Average experience and hours/day spent on handling animal was reported respectively 22±15yrs (median age of 20yrs) and 5±2 hrs. It was observed that median value for types of breeds of animals was five (IQR= 3 to 8) which ranged from 1 to 70 animals. Different breeds of animals reported by the livestock keepers, which included Buffalo 64%, Cow 38%, Goat 20%, Dog 5% and Sheep & Bulls 4%.On inquiring about their perception on acquiring by virtue of engagement in animal handling can be a cause of the disease was reported by only one-third of participants. Knowledge about common zoonotic reported for rabies (11%), respiratory disease (10%) followed by vector born disease (7%) and skin disease (1.2%). Average knowledge on the mode of transmission of Z/D/S was reported only 4.1%.The study also documented the commonly used methods for prevention of zoonotic disease, most common practice was found hand washing practice (83%) followed by avoiding contact to animal placenta with naked hands (68%).ConclusionsThe prevalence of self-reported Z/D/S was underestimated when compared to other studies within India. One of the common reasons could be poor awareness of Z/D/S amongst high-risk groups. Results suggest that it is important to initiate screening and improve the awareness of Z/D/S amongst animal handlers to improve the reporting of Z/D/S.

A Novel Anti‐Inflammatory Agent for the Management of Preeclampsia

Preeclampsia (PE) is a hypertensive disorder of pregnancy which impacts approximately 5–8% of all pregnancies worldwide and is the leading cause of maternal and fetal morbidity and mortality. PE is characterized by new onset of hypertension, typically after 20 weeks gestation, in addition to at least one other symptom such as proteinuria, liver dysfunction or low platelet count. Though the etiology of PE has yet to be elucidated, placental ischemia is believed to be central to the development of this disease. In response, the hypo‐perfused placenta releases a number of factors into the maternal circulation, including inflammatory cytokines like TNFα. Targeting this inflammatory response has been shown to lower blood pressure and improve endothelial function in preclinical PE models. We have recently developed a synthetic polypeptide drug carrier, elastic‐like polypeptide (ELP), for delivery of drugs during pregnancy. ELP prolongs the half‐life of small peptide‐based therapeutics in the circulation and prevents fetal exposure of the agents by preventing placental transfer to the fetal circulation. In order to target placental inflammation, we have produced an ELP‐ fusion protein (ELP‐P50) targeting a master regulator of inflammation, nuclear factor‐ κB (NF‐κB). Because NF‐κB has been shown to be elevated in preeclamptic women and the immune system has been shown to be activated in this disease, we tested the hypothesis that administration of ELP‐P50 would attenuate the maternal hypertension and inflammation in the reduced uterine perfusion pressure (RUPP) model of pregnancy‐induced hypertension. Compared to the sham operated rat, RUPP rats have significantly higher MAP (99 ± 4 mmHg vs 122 ± 3 mmHg; p< 0.001). Administration of ELP‐P50 from GD14–19 in RUPP rats significantly reduces MAP, at both low 50 mg/kg (122 ± 3 mmHg vs 111 ± 2 mmHg; p< 0.05) or high 75 mg/kg (122 ± 3 mmHg vs 111 ± 2 mmHg; p< 0.05) dose. As TNFα is a known target upregulated by NF‐κB, we measured the effects of ELP‐P50 on placental production of TNFα. As measured by ELISA, there was a trend for increased TNFα in RUPP animals compared to shams (4.4 ± 0.7 μg/mL/mg vs 3.2 ± 0.3 μg/mL/mg total protein; p= 0.15). When the RUPP animals were treated with the ELP‐P50, there was a significant reduction in TNFα. There was a 50% reduction in placental TNFα in both animals receiving 50 mg/kg (2.2 ± 0.3 μg/mL/mg vs 4.4 ± 0.7 μg/mL/mg total protein; p<0.05), and the animals receiving 75 mg/kg of ELP‐P50 (2.2 ± 0.1 μg/mL/mg vs 4.4 ± 0.7 μg/mL/mg total protein; p< 0.05). It is known that TNFα can also act as a cytokine to promote immune cell infiltration. For this reason, we measured T‐cell populations in the animal placentas by flow cytometry. There were no significant differences, however, in either helper T‐cells or cytotoxic T‐cells suggesting the NF‐κB activation has no impact on these resident immune cells. ELP‐P50 is able to significantly reduce blood pressure and lower levels of placental TNFα in the rodent RUPP model of placental ischemia. The fact that blood pressure is not completely returned to normal, however, unsurprisingly suggests that there are other pathways involved in the development of hypertension in the RUPP model. Future studies will further characterize the mechanism of action of this agent and confirmatory studies will be performed in other experimental models of PE to advance the translation of this agent as a possible therapeutic agent for PE.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Study of embryotoxic effects of intranasally administred desloratadine on laboratory animals.

The study was conducted to detect possible changes in embryogenesis and negative effects of third generation antihistamine – desloratadine – after intranasal administration of 1.3 mg/m 3 and 13.0 mg/m 3 of the substance to laboratory animals during their prenatal period. In these circumstances, desloratadine does not cause any significant changes of embryogenesis parameters . Macroscopic examination of the fetus and placenta in animals of experimental groups did not reveal any pathology or physiological deviations from the norm. 13.0 mg/m 3 concentration of the drug caused a decrease in the weight of embryos in comparison with control group of animals and physiological data , despite a well developed, without visible pat h ology, placenta. This neces ­ sitates a n in-depth study o f possible teratogenic effects of intranasally administred desloratadine to laboratory animals.

Green tea (-)-epigallocatechin gallate inhibits the growth of human villous trophoblasts via the ERK, p38, AMP-activated protein kinase, and protein kinase B pathways.

Green tea catechins, especially (-)-epigallocatechin gallate (EGCG), have been reported to circulate in the placenta of animals and blood of humans after consumption. Whether EGCG regulates activity of human villous trophoblasts (HVT) is unknown. This study investigated the pathways involved in EGCG modulation of trophoblast mitogenesis. EGCG inhibited trophoblast proliferation in a dose-dependent and time-dependent manner, as indicated by the number of cells and incorporation of bromodeoxyuridine (BrdU). EGCG was more effective than other green tea catechins in inhibiting cell growth. EGCG also increased the phosphorylation of the MAPK pathway proteins, ERK1/2, and p38, but not JNK. Furthermore, EGCG had no effects on the total amounts of ERK1/2, p38 MAPK, and JNK proteins. This suggests that EGCG selectively affects particular MAPK subfamilies. Pretreatment with specific inhibitors of ERK1/2, p38 MAPK, and AMP-activated protein kinase (AMPK) antagonized EGCG-induced decreases in both cell number and BrdU incorporation. These inhibitors also blocked EGCG-induced increases in the levels of phospho-ERK1/2, phospho-p38, and phospho-AMPK proteins, respectively. Moreover, EGCG was similar to the phosphatidylinositol 3-kinase inhibitors wortmannin and LY-294002 to decrease protein kinase B (AKT) phosphorylation, cell number, and BrdU incorporation. These data imply that EGCG inhibits the growth of HVT through the ERK, p38, AMPK, and AKT pathways.

FcRn Expression on Placenta and Fetal Jejunum during Early, Mid-, and Late Gestation in Minipigs.

Developmental toxicity testing of therapeutic antibodies is most often conducted in nonhuman primates owing to lack of cross-reactivity in other species. Minipigs may show cross-reactivity for some humanized antibodies but have not been used for developmental toxicity testing due to an assumed lack of embryo-fetal exposure. Unlike in humans, maternal IgGs do not cross the porcine placenta to reach the fetus. Some humanized IgGs, however, have a higher affinity for the neonatal Fc receptor (FcRn) and are more likely than endogenous antibodies to cross the placenta of animals. The major site of prenatal IgG transfer is the placenta, though FcRn in fetal intestine could also uptake maternal IgGs from swallowed amniotic fluid. Using immunohistochemistry andin situhybridization in this experiment, FcRn was found in minipig placenta and fetal intestine during early, mid-, and late gestation. To date, however, fetal exposure to maternally administered IgGs has never been demonstrated in the minipig.

FcRn expression on placenta and fetal jejunum during early, mid and late gestation in minipigs

Developmental toxicity testing of therapeutic antibodies is most often conducted in nonhuman primates owing to lack of cross-reactivity in other species. Minipigs may show cross-reactivity for some humanized antibodies but have not been used for developmental toxicity testing due to an assumed lack of embryo-fetal exposure. Unlike in humans, maternal IgGs do not cross the porcine placenta to reach the fetus. Some humanized IgGs, however, have a higher affinity for the neonatal Fc receptor (FcRn) and are more likely than endogenous antibodies to cross the placenta of animals. The major site of prenatal IgG transfer is the placenta, though FcRn in fetal intestine could also uptake maternal IgGs from swallowed amniotic fluid. Using immunohistochemistry andin situhybridization in this experiment, FcRn was found in minipig placenta and fetal intestine during early, mid-, and late gestation. To date, however, fetal exposure to maternally administered IgGs has never been demonstrated in the minipig.

Are animal models useful or confusing in understanding the human feto-maternal relationship? A debate

The proposition “This house agrees that the proper study of man is woman” was debated. For those negating the proposition, the alternative was that “animal models are useful in understanding the human feto-maternal relationship.” Evidence for the proposition emphasized molecular and structural differences between the human and animal placenta and placentation. Evidence against the proposition and in favor of the alternative focused on functional and structural homologies, emphasizing that different molecules could be used in humans to achieve similar functional effects seen in animal (e.g., mouse) models. It was agreed that one always needed to test the validity of animal data by studying humans. The advantages and limitations of animal models were discussed.

And Baby Makes Three: Genomic Imprinting in Plant Embryos

And Baby Makes Three: Genomic Imprinting in Plant Embryos

Comparative analysis of binding affinities to epidermal growth factor receptor of monoclonal antibodies nimotuzumab and cetuximab using different experimental animal models

Although pharmaco/toxicological studies have always been conducted in pharmacologically relevant species in which the test material is pharmacologically active, the very specificity of many biopharmaceuticals could present challenges in the identification of a relevant species for pharmaco/toxicological studies. Alternative approaches may improve the predictive value of preclinical assessments of species-specific biopharmaceuticals. This could lead to improved decision-making, reduce the number of experimental animals by eliminating non-relevant studies, and decrease the time and cost involved in the drug development process. As an alternative to utilizing traditional animal models, this study investigated the activity of human EGF and the anti-EGF receptor monoclonal antibodies nimotuzumab and cetuximab using the placenta microsomal fraction of different experimental animals. Ligand–receptor binding curves were obtained from the different experimental animal models, and binding constants were calculated based on the Scatchard plots. The constants for human and monkey EGF receptor expressed on the placental extract showed a K a < 10 −8 M, while rabbits, mice and rats showed a K a > 10 −8 M. The K a values obtained from animal placentas show that Macaca fascicularis and Cercopitecus aethiops monkeys are relevant species for studying the pharmaco/toxicological properties of nimotuzumab and cetuximab.

Effect of zinc supplementation in pregnant mice during experimental Trypanosoma cruzi infection

Zinc is an essential micronutrient and has significant effects on human growth, development, and immune function. Zinc supplementation or deficiency may affect the course of infection. Zinc enhances immune response against a wide range of viral, bacterial, and parasitic pathogens. In the present study, we investigated the effects of zinc sulphate (ZnSO 4) supplementation (20 mg/kg/day) during pregnancy in mice, Swiss Webster strain infected by the Y strain of Trypanosoma cruzi. Oral supplementation of zinc sulphate in pregnant and non-pregnant infected animals did not affect the count of blood parasites as well as tissue parasitism in the heart, liver, and spleen. Zinc supplementation did not alter female body weight, the length of fetuses and neonates, placental size/weight and mortality rate. Among zinc supplied animals, no significant plasmatic zinc concentrations were observed. Concerning to tissue zinc concentrations, only the liver displayed enhanced values as compared to other organs. For placental parasitism, zinc supplied group displayed a significant decrease in amastigote burdens ( P < 0.05). However due to the reduced number of parasite burdens in placenta of animals supplied with zinc, these data suggest that zinc was partially effective in up-regulating the host’s immune response against parasite, probably attenuating the infection in fetuses.

Azithromycin Inhibits Vertical Transmission of Toxoplasma gondii in Calomys callosus (Rodentia: Cricetidae)

Toxoplasma gondii infection during pregnancy may cause severe consequences to the embryo. Current toxoplasmosis treatment for pregnant women is based on the administration of spiramycin or a drug combination as sulphadiazine-pyrimethamine-folinic acid (SPFA) in cases of confirmed fetal infection. However, these drugs are few tolerated and present many disadvantages due to their toxic effects to the host. The aim of this study was to evaluate the effectiveness of different treatments on the vertical transmission of T. gondii, including azithromycin, Artemisia annua infusion, spiramycin and SPFA in Calomys callosus as model of congenital toxoplasmosis. C. callosus females were perorally infected with 20 cysts of T. gondii ME49 strain at the day that a vaginal plug was observed (1st day of pregnancy – dop). Treatment with azithromycin, A. annua infusion, and spiramycin started at the 4th dop, while the treatment with SPFA started at the 14th dop. Placenta and embryonic tissues were collected for morphological and immunohistochemical analyses, mouse bioassay and PCR from the 15th to 20th dop. No morphological changes were seen in the placenta and embryonic tissues from females treated with azithromycin, spiramycin and SPFA, but embryonic atrophy was observed in animals treated with A. annua infusion. Parasites were found in the placenta and fetal (brain and liver) tissues of animals treated with SPFA, A. annua infusion and spiramycin, although the number of parasites was lower than in non-treated animals. Parasites were also observed in the placenta of animals treated with azithromycin, but not in their embryos. Bioassay and PCR results confirmed the immunohistochemical data. Also, bradyzoite immunostaining was observed only in placental and fetal tissues of animals treated with SPFA. In conclusion, the treatment with azithromycin showed to be more effective, since it was capable to inhibit the vertical transmission of T. gondii in this model of congenital toxoplasmosis.

Drug misuse during pregnancy and fetal toxicity

Drug misuse during pregnancy and fetal toxicity

Antibacterial, anti-inflammatory and mutagenic effects of some medicinal plants used in South Africa for the treatment of wounds and retained placenta in livestock

Crude dichloromethane and 90% methanolic extracts of plants used traditionally in the treatment of wounds and retained placenta were screened for their antibacterial, anti-inflammatory (cyclooxygenase-1 and-2) activities and investigated for potential mutagenic effects. Antibacterial activity was evaluated using the micro-dilution assay. The bacterial strains used were Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853). DCM extracts of Dicerocaryum eriocarpum, Pterocarpus angolensis, Ricinus communis and Schkuhria pinnata exhibited the highest antibacterial activity. In the anti-inflammatory assay, dichloromethane extracts of stems of Cissus quadrangularis and roots of Jatropha zeyheri showed selective inhibition of COX-2 (75% and 77%), while dichloromethane extracts of the shoots of S. pinnata showed selective inhibition of COX-1. None of the plant extracts were mutagenic in the Salmonella typhimurium Ames test (strain TA98). The results suggest that most plants used traditionally for treating wounds and retained placenta in animals are effective in combating infection and reduction of pain. Lack of mutagenicity suggests that these plants are probably safe for use.

Rat Spongiotrophoblast-specific Protein Is Predominantly a Unique Low Sulfated Chondroitin Sulfate Proteoglycan

We have previously demonstrated that the human placenta contains a uniquely low sulfated extracellular aggrecan family chondroitin sulfate proteoglycan (CSPG). This CSPG is a major receptor for the adherence of Plasmodium falciparum-infected red blood cells (IRBCs) in placentas, causing pregnancy-specific malaria. However, it is not known whether such low sulfated CSPGs occur in placentas of other animals and, if so, whether IRBCs bind to those CSPGs. In this study, we show that rat placenta contains a uniquely low sulfated extracellular CSPG bearing chondroitin sulfate (CS) chains, which comprise only approximately 2% 4-sulfated and the remainder nonsulfated disaccharides. Surprisingly, the core protein of the rat placental CSPG, unlike that of the human placental CSPG, is a spongiotrophoblast-specific protein (SSP), which is expressed in a pregnancy stage-dependent manner. The majority of rat placental SSP is present in the CSPG form, and only approximately 10% occurs without CS chain substitution. Of the total SSP-CSPG in rat placenta, approximately 57% is modified with a single CS chain, and approximately 43% carries two CS chains. These data together with the previous finding on human placental CSPG suggest that the expression of low sulfated CSPG is a common feature of animal placentas. Our data also show that the unique species-specific difference in the biology of the rat and human placentas is reflected in the occurrence of completely different CSPG core protein types. Furthermore, the rat SSP-CSPG binds P. falciparum IRBCs in a CS chain-dependent manner. Since IRBCs have been reported to accumulate in the placentas of malaria parasite-infected rodents, our results have important implications for exploiting pregnant rats as a model for studying chondroitin 4-sulfate-based therapeutics for human placental malaria.

Final report on the safety assessment of human placental protein, hydrolyzed human placental protein, human placental enzymes, human placental lipids, human umbilical extract, placental protein, hydrolyzed placental protein, placental enzymes, placental lipids, and umbilical extract.

Various proteins, lipids, or other extracts from human or other animal placentas are described as cosmetic ingredients. Human Placental Protein comprises protein derived from human placentas. Placental Protein is derived from animal placentas. Similarly, Human Placental Lipids and Placental Lipids are the lipid fractions from the same source materials. Hydrolyzed Human Placental Protein and Hydrolyzed Placental Protein are produced from the respective protein extracts by acid, enzyme, or other hydrolysis methods. Human Placental Enzymes and Placental Enzymes are enzymes obtained by aqueous extraction of human or other animal placental material. Human Umbilical Extract and Umbilical Extract are unspecified extracts of material from human or other animal umbilical cords. Different materials called Human Placental Extracts and Placental Extracts, assumed to contain estrogenic hormones or other biologically active substances, are not recognized as cosmetic ingredients, even though the use of these ingredients in cosmetics have been reported to the Food and Drug Administration (FDA). Human-derived ingredients are prohibited from use under the provisions of the European Union cosmetics directive based on concerns about transmission of human spongiform encephalopathies and viral diseases, for example, human immunodeficiency virus (HIV). Umbilical Extract has precedent for unrestricted use in Japan, except for certain products. Most of these ingredients are described as hair-conditioning agents and miscellaneous skin-conditioning agents, although the umbilical extracts function as biological additives in cosmetics. Of the human-derived ingredients, only Human Placental Protein is currently reported to be used. Animal-derived placental proteins, hydrolyzed proteins, lipids, and enzymes were all currently reported to be used. No current uses of the umbilical extracts were reported. Most of the available data relates to placental derivatives that appear to have estrogenic or other biological activity. The one clinical study that appears to utilize proteinaceous material only reported no irritant reaction. Clearly, the available data are insufficient to support safety of these ingredients in cosmetics. The additional data needed include (1) skin sensitization at concentration of use; (2) gross pathology and histopathology in skin and other major organ systems associated with repeated exposures, and dermal reproductive and developmental toxicity data; (3) photosensitization; (4) one genotoxicity assay in a mammalian system; if positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods may be needed; (5) ocular toxicity, if available. Any studies should be done on all ingredients unless chemical analysis data show similarity among ingredients. Because there is confusion and concern about the use of substances with estrogenic or other biological activity in cosmetic formulations, it was concluded that none of these ingredients used in cosmetics should deliver any metabolic/endocrine activity. In addition, any current use of these ingredients should be free of detectable pathogenic viruses or infectious agents.