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Blood ammonia levels and hepatic encephalopathy induced by CCl4 in rats.

An investigation of the mechanism of development of hepatic encephalopathy induced by CCl4 was performed in rats. CCl4 (1.0 ml/kg three times per week for over 10 weeks) caused hepatic encephalopathy in 80% of the treated rats. Accompanying the hepatic encephalopathy were hematemesis, abdominal dropsy, and hyperammonemia, conditions observed in hepatic coma patients. The blood ammonia levels were tremendously increased in only those rats with hepatic encephalopathy. Hepatic activities of carbamylphosphate synthetase (CPS) and argininosuccinate synthetase (ASS), important enzymes of the urea cycle, were significantly inhibited by CCl4. However, the causality between the inhibition of CPS or ASS activity and the increase in blood ammonia levels was not observed. On the other hand, the content of ATP, which is a substrate of CPS and ASS, was decreased by 60% in liver of rats with hepatic encephalopathy. The activity of Mg2+-ATPase which can decompose hepatic ATP was increased by 60 and 300% in mitochondria and microsomes, respectively, of livers of rats with CCl4-induced encephalopathy. There was a good correlation between the decreased hepatic ATP content and the increased mitochondrial Mg2+-ATPase activity. Furthermore, there was also a good correlation between the increase in blood ammonia levels and the increase in Mg2+-ATPase activity in microsomes. These findings suggest that hyperammonemia, which was produced by the decrease in hepatic content and by the inhibition of CPS and ASS, may play an important role in induction of hepatic encephalopathy.

Adenosine Triphosphate↗

A Globosus amorphus from an in vitro fertilized embryo transferred to a Japanese black cow.

A Globosus amorphus along with a living calf was encountered following the transfer of blastocysts obtained by in vitro fertilization of in vitro-matured follicular oocytes in Japanese black cattle. Two embryos obtained 9 days after in vitro fertilization developed into either a hatched blastocyst with distinct inner cell mass or an expanded blastocyst with indistinct inner cell mass. The embryos were loaded into a 0.25-ml plastic straw and were nonsurgically transferred to the uterus of a heifer on Day 8 (Day 0 = estrus). On Day 75, a twin pregnancy was ultrasonically diagnosed in the right uterine horn, in which a live fetus with distinct limbs and a concomitant ovoid mass were detected. On Day 287, the dam developed parturient paralysis with dropsy of the fetal membranes. By palpation per rectum an ovoid mass was detected in the body of the uterus [corpus uteri] and a larger live fetus was in the uterine horn. A cesarean section was performed to extract a live fetus and a Globosus amorphus. The live fetus was female with the 60, XX female complements.

Journal Article↗

Sanguinarine and chelerythrine: assessment of safety on pigs in ninety days feeding experiment.

Sanguinaria canadesis, Chelidonium majus and Macleya cordata have been used for centuries as alternative medicines. Currently the extracts from these medicinal plants are components of veterinary and human phytopreparations, and of oral-hygiene agents. Sanguinarine and chelerythrine (SA/CHE) are biologically active components of these extracts. They display distinct antibacterial and anti-inflammatory properties, but, on the other hand, they have been reported as having adverse effects - genotoxicity and hepatotoxicity. This paper is aimed at evaluation of the effects of daily administration of the extract from Macleya cordata (2 mg and 100 mg in 1 kg feed, sanguinarine:chelerythrine 3:1) in the diet on the health status of swine. After 90-day administration, alkaloids were retained to a different extent in tissues. The highest SA/CHE retention was detected in the gingiva (0.55 microg/g) and liver (0.15 microg/g), no SA/CHE were detected in muscles. Plasma SA levels attained 0.11 microg/ml. Treated animals did not display any results of hematological, biochemical or histological assay different from controls. A (32)P-postlabeling assay proved that no DNA-adducts with SA/CHE were detected in pig livers. We did not observe any symptom linked to epidemic dropsy syndrome often attributed to sanguinarine. In conclusion, an average daily oral dose of alkaloids up to 5 mg per 1 kg animal body weight proved to be safe.

Alkaloids↗

In vivo DNA damaging potential of sanguinarine alkaloid, isolated from argemone oil, using alkaline Comet assay in mice.

Consumption of mustard oil contaminated with argemone oil is well known to cause clinical manifestation referred to as "Epidemic Dropsy". Our prior studies have shown that argemone oil produces genotoxic effects in mice [Ansari, K.M., et al., 2004. Int. J. Cancer 112, 890]. Since, sanguinarine alkaloid is the major component of argemone oil, the in vivo DNA damaging potential of the isolated alkaloid was investigated in blood and bone marrow cells of mice using alkaline Comet assay. Swiss albino male mice were given single intraperitoneal administration of 1.35, 2.70, 5.40, 10.80 and 21.60 mg sanguinarine alkaloid/kg b wt., while controls were treated with saline in the same manner. The results revealed a dose dependent increase in DNA damage in blood and bone marrow cells following 24 h treatment of sanguinarine alkaloid. All the three parameters of Comet assay including olive tail moment (OTM), tail length and tail DNA showed significant (p<0.05) increases in blood and bone marrow cells at respective doses of 10.80 and 5.40 mg alkaloid/kg b wt. However, some of the parameters were significantly increased even at lower doses of sanguinarine alkaloid (2.70 mg/kg b wt.). The frequency of cells exhibiting greater DNA damage were found to be increased by sanguinarine alkaloid in a concentration dependent manner. These results indicate that single exposure of sanguinarine alkaloid causes DNA damage in blood and bone marrow cells of mice, which could be responsible for the genotoxicity of argemone oil.

Alkaloids↗

Sanguinarine: an evaluation of in vivo cytogenetic activity.

Sanguinarine (SG), a benzophenanthridine alkaloid, has been shown to possess anti-microbial, anti-inflammatory and antioxidant properties. In the UK and USA its salts has been in use in mouthwashes and toothpastes to inhibit dental plaque and improve gingival health. In India and Nepal consumption of mustard oil contaminated with argemone seeds containing sanguinarine, was associated with "dropsy" syndrome. In the present study, SG was evaluated in vivo in mouse bone marrow cells for its ability to induce clastogenicity and DNA damage in terms of increased sister chromatid exchange (SCE) frequencies. Doses of 5, 10, and 15 mg/kg body weight of SG given intra peritoneally induced a positive dose-dependent significant clastogenicity and SCE frequency increases (trend test alpha < or = 0.05). The minimum effective concentration to induce clastogenic and DNA damage was 10mg of SG/kg body weight. In addition to examining SCEs, the BrdUrd-differential technique was utilized to assess the effect of SG on cell replication. The analysis revealed that SG treatment did not significantly affect the distribution of cells among the different phases of the cell cycle. The proliferation rate index and average generation time data were statistically non-significant. This indicated that the alkaloid was not cytotoxic to the bone marrow cells at the doses tested. Based on the results of the present findings, the use of this alkaloid should be restricted.

Alkaloids↗

Use of PCR-restriction fragment length polymorphism for the identification of zoonotic mycobacteriosis in zebrafish caused by Mycobacterium abscessus and Mycobacterium chelonae.

Skin ulcers, scoliosis, and dropsy-like scale edema were observed in laboratory-maintained zebrafish. Affected fish had multifocal granulomas not only in internal organs such as the liver, intestine, genital organs, kidney, muscle, and spleen but also in the fin, epithelium, gills, and sclera of the eyes. Large numbers of acid-fast-rod-shaped bacteria were observed within the necrotic centers of well-demarcated, multifocal granulomas with Gram's stain and Ziehl-Neelson's stain. The size of the Mycobacterium spp. was 1-2 microm x 2-3 microm with a double-layered cell wall, based upon electron-microscopical features. Definitive diagnosis of these outbreaks was obtained by culture on selective media followed by PCR-restriction fragment length polymorphism analysis (PRA) of the rpoB gene for species identification. The amplified 360-bp products of the rpoB gene of mycobacteria isolated from zebrafish were digested with MspI restriction enzyme, which revealed unique band patterns matching those of Mycobacterium abscessus and Mycobacterium chelonae which are responsible for skin and soft tissue infection caused by rapidly growing mycobacteria in humans. This is the first documentation of the precise identification of zoonotic non-tuberculous mycobacteria isolated from laboratory-maintained zebrafish by the PRA of the rpoB gene; this study thus provides a great deal of useful epidemiological information and reduces the likelihood that epizootics will occur.

Animals↗

Abnormal expression of matrix metalloproteinase-2 and -9 in interspecific pregnancy of rat embryos in mouse recipients.

The high failure rate of interspecific pregnancy is a major obstacle to the successful interspecific cloning of mammals. Embryo transfer between rats and mice provides a unique model for studying the causes of such failures. Previous research has shown that the upper time limit for the survival of rat embryos in mouse uteri was the seventh day of pregnancy (Day 7). To study the reasons for the failure of interspecific pregnancy between rats and mice, we transferred rat blastocysts into mouse uteri on the third day of pseudopregnancy. Unexpectedly, intact rat embryos could still be observed in mouse uteri on Day 9 and the implantation rate was as high as 30.6%. However, compared with mouse embryos, the further development of transferred rat embryos in mouse uteri was retarded. On Day 10, transferred rat embryos shrank with much blood. From Day 11 on, they lost their intact structure and the recipient uteri developed dropsy. On Day 12, the embryos shrank further and completely separated from the mouse uteri. By Day 13, they had been absorbed without any remains. In an in vitro co-culture (CT) system, the attachment rate of rat embryos on a monolayer of mouse uterine epithelial cells was similar to that of mouse embryos, but the outgrowth rate of rat embryos was significantly lower. Further investigation by gelatin zymography showed that matrix metalloproteinase-2 (MMP-2) and metalloproteinase-9 (MMP-9) activities in transferred rat embryos was significantly less than in mouse embryos. The same result was obtained in the in vitro CT assay. These results suggest that rat embryos can complete adhesion but not the invasion when transferred into mouse uteri. The reduced invasive ability, and especially, the associated reduction of MMP-2 and -9 activity, is one of the reasons for the failure of interspecific pregnancy.

Animals↗

Biodegradation and distribution of water-soluble chitosan in mice.

Randomly 50% deacetylated chitin, called Chi, was examined on the biodegradability, body distribution and urinary excretion after the intraperitoneal (ip) administration to mice. These characteristics were investigated using fluorescein isothiocyanate (FITC)-labeled Chi (FTC-Chi). The in vitro biodegradability was investigated by incubation with lysozyme and murine plasma and urine. The degradation of Chi or FTC-Chi was accelerated by lysozyme, plasma and urine. The molecular weight was checked by gel-chromatography. The degradation product showed a fairly small molecular weight and contained no FTC-Chi of a large one. The body distribution and urinary excretion of FTC-Chi were investigated at 1, 14 and 24 h after the ip injection to mice. FTC-Chi moved fast to the kidney and urine, and was scarcely distributed to the liver, spleen, abdominal dropsy and plasma. Most of FTC-Chi was excreted into urine after 14 h, and the molecular weight of the excreted FTC-Chi was as small as that of the product obtained by the long in vitro incubation. Therefore, Chi is considered to be highly biodegradable and easily excreted in urine, and further it is suggested to have no problem on accumulation in the body; however, at the same time, Chi is found not to operate as a polymer support showing long retention in the body.

Acetylation↗

Argemone mexicana poisoning: autopsy findings of two cases.

Epidemic dropsy, a disease due to Argemone mexicana poisoning, is characterized by pathological accumulation of diluted lymph in body tissues and cavities. Recently, the largest epidemic of the disease in India affected Delhi and its neighboring states during the months of August-September 1998. Over 3000 persons fell ill, and more than 65 died in the state of Delhi alone. Two cases belonging to the same family died, out of the large number of cases admitted in this tertiary care teaching hospital situated in eastern part of Delhi. Autopsy findings of these two cases are presented and discussed here along with the review of toxicity due to this poisoning.

Autopsy↗

Scuticociliata infection in the weedy sea dragon Phyllopteryx taeniolatus.

The weedy sea dragon Phyllopteryx taeniolatus at an aquarium in Kanagawa Prefecture were found infected by protozoan ciliate, 2001. The infected fish in particular, showed sloughing of the epidermis. Fish with intense infections showed sloughing of the dorsal fin, depigmentation of skin, anal distension and accumulation of ascitic fluid in the body cavity. In biopsies, ciliates were detected only in fresh mounts of abdominal dropsy and in the mucus on the body surface. Histopathological studies revealed ciliates mainly infected the dermis, and induced extensive detachment of the epidermis from the skin. Based on the arrangement and shape of the buccal structure and the number of somatic ciliature, ciliates isolated from the fishes belonged to the order Scuticociliatida. We discuss the major factors that bring about the death of weedy sea dragons.

Animals↗

Treatment of heart failure according to William Stokes: the enchanted mercury.

BACKGROUND: It was not until 1919 that the diuretic properties of mercury were observed in patients with syphilis; in the same year the beneficial effects of mercurial diuretics were shown in a patient with severe rheumatic heart disease and anasarca. However, mercury had been used much earlier for the treatment of dropsy without clear guidelines. In this article we describe William Stokes' insights into the treatment of heart failure, focusing on the beneficial diuretic properties of mercury. METHODS: We reviewed the chapter "Treatment of the Weak and Probably Dilated Heart in Connexion With Enlargement of the Liver and Pulmonary Disease" in William Stokes' famous treatise The Diseases of the Heart and the Aorta. CONCLUSIONS: Stokes makes several important clinical observations. First, he provides precise guidelines on when and how to use mercury in these patients. Second, he realizes the importance of mercury for the treatment of decompensated heart failure. Stokes recognizes the cyclical nature of frequent decompensation in congestive heart failure, the relationship of clinical deterioration and reduced urine output, and the importance of reestablishing urinary flow to ameliorate dyspnea. Third, he attempts to define the mechanism of action "... if any of the characteristic action of mercury can be perceived unless we include diuresis." Finally, he gives interesting guidelines on the dosage and side effects of mercury. These observations on the treatment of "congestive" heart failure are an important contribution to the understanding of heart failure pathophysiology and the design of prescription regimens for this disease.

Heart Failure↗

[Short rib-polydactyly syndromes].

The authors report on a newborn which died only a few hours after birth. It manifested generalized dropsy and ascites, a central upper lip cleft, narrow thorax, severe dysraphia, short limbs but normal-length trunk, and brachydactyly. Particularly striking radiologic findings were the extremely short, horizontal ribs and a shortening of the long bones, with rounded calcification zones. On the basis of comparison with other cases of short rib-polydactyly syndromes (SRPS) and other chondrodysplasias, this case was classified as Majewski's syndrome, even though there was no polydactyly and the shortness of the tibiae was not as extreme as in typical cases.

Adult↗

Improving mental health through nutrition: the future.

Tell me what you eat, and I will tell you what you are (Anthelme Brillat-Savarin). When I behold a fashionable table set out in all its magnificence, I fancy that I see gouts and dropsies, fever and lethargies, with other innumerable distempers, lying in ambuscade among the dishes. Nature delights in the most plain and simple diet. Every animal, but man, keeps to one dish. Herbs are the food of this species, fish of that, and flesh of a third. Man falls upon everything that comes in his way; not the smallest fruit or excrescence of the earth, scarce a berry or a mushroom can escape him (Joseph Addison). The pleasures of the palate deal with us like the Egyptians thieves, who strangle those whom they embrace (Seneca). Let food be your medicine and medicine be your food (Hippocrates).

Animals↗

Digoxin 1785-1985. I. Two hundred years of digitalis.

This year we are celebrating the bicentenary of the publication, by William Withering, of An Account of the Foxglove and Some of its Medicinal Uses with Practical Remarks on Dropsy and Other Diseases (1). During these two hundred years digitalis has constantly been to the fore of medical thinking and it is appropriate that we should look back and examine the contributions which studies of this drug have made to medicine as we know it today. Some of the studies have been at the centre of fierce controversy and others have been of seminal importance in the development of new concepts.

Biological Availability↗

The identification and separation of Aeromonas liquefaciens from Pseudomonas fluorescens and related organisms occurring in diseased fish.

Taxonomy of the motile species of the genus Aeromonas is briefly discussed. It is suggested that Aeromonas organisms, isolated from outbreaks of red mouth of trout, red sore of pike, infectious abdominal dropsy and hemorrhagic septicemia of warm water fish, and which show acid and gas in glucose broth, production of 2,3-butanediol hydrogen sulfide from motility sulfide medium, presence of cytochrome oxidase, and hydrolysis of starch, be designated as Aeromonas liquefaciens. These tests also serve to differentiate A. liquefaciens from fish-pathogenic Pseudomonas fluorescens and from enteric bacteria.

Aeromonas↗

The kidney in ancient Egyptian medicine: where does it stand?

Driven by their deep-seated desire for eternal life in a healthy body, ancient Egyptians were one of the first civilizations to begin collecting and recording medical lore and medicinals that were effective for a healthy body. With its religious origins, medical care was initially provided by priests, but evolved over time into an independent discipline practiced by the swnw (sounou) or physician. What has been preserved of their knowledge in extant medical papyri reflects the great capacity of Egyptians for practical achievement in treating symptoms, but lacks the abstract thought that was to come with the advent of the more rational Greek medicine. The number of prescriptions and incantations for the management of urinary disorders (hematuria, retention, frequency, infection) and dropsy that are mentioned in extant medical papyri likely reflect the frequency with which these problems were encountered. Urine was thought to be formed in the region of the bladder, by a process considered akin to purification. Available studies on preserved mummies indicate that kidney disease was not uncommon. Whether a functional role of the kidney was appreciated at all is highly doubtful. On the other hand, the available evidence suggests an awareness of the kidney (ggt) to which was ascribed a mythological role that may well account for why the kidneys and the heart were the only organs not removed during the process of mummification.

Egypt, Ancient↗

Edema in the Corpus Hippocraticum.

In this paper, we analyze the collection of ancient Greek treatises ascribed to Hippocrates (460; between 371 and 350 BC), in order to determine whether or not edema can be traced. As a result of reading these works on the Greek text, we recognize some symptoms of edema in those called oidêma (swelling) and udrôps (dropsy) in the oldest treatises of the Corpus; in some cases, it seems also possible to recognize its description as the uremic coma. The dysfunction of edema had not been identified as such, however, even though the phenomena associated with the above symptoms received a specific explanation, which was fully hypothetical. This theoretical explanation also justifies the therapies prescribed for the treatment of the phenomena among which edema appears. Significantly enough, the treatment changed during a period which corresponds to that of Hippocrates' life: it changes from the four-quality system to that one of the four humors, but not necessarily under the influence of Hippocrates himself.

Edema↗

The low countries - 16th/17th century.

Andreas Vesalius and Jan Baptist Van Helmont are the two major personalities who contributed substantially and in a different way to the early development of renal anatomy/physiology of the 16th/17th century in the Southern Low Countries. The importance of A. Vesalius' publication 'de humani corporis fabrica libri septem' cannot be overestimated. The kidney was an intriguing organ to Vesalius, the function of which he could not fully grasp. J.B. Van Helmont was the first to demonstrate the importance of the measurement of the specific gravity of the urine and relating it to physiological and pathophysiological conditions. He made accurate clinical observations supported by autopsy examinations concerning the role of the kidney in the generation of dropsy.

Belgium↗