Navigating the multifaceted intricacies of the Na+-Cl- cotransporter, a highly regulated key effector in the control of hydromineral homeostasis.

The Na+-Cl- cotransporter (NCC; SLC12A3) is a highly regulated integral membrane protein that is known to exist as three splice variants in primates. Its primary role in the kidney is to mediate the cosymport of Na+ and Cl- across the apical membrane of the distal convoluted tubule. Through this role and the involvement of other ion transport systems, NCC allows the systemic circulation to reclaim a fraction of the ultrafiltered Na+, K+, Cl-, and Mg+ loads in exchange for Ca2+ and [Formula: see text]. The physiological relevance of the Na+-Cl- cotransport mechanism in humans is illustrated by several abnormalities that result from NCC inactivation through the administration of thiazides or in the setting of hereditary disorders. The purpose of the present review is to discuss the molecular mechanisms and overall roles of Na+-Cl- cotransport as the main topics of interest. On reading the narrative proposed, one will realize that the knowledge gained in regard to these themes will continue to progress unrelentingly no matter how refined it has now become.

A simple, inexpensive, life-saving way to perform iterative laparotomy in patients with severe intra-abdominal sepsis.

Between 1 June 1993 and 31 December 1998, 17 patients underwent temporary abdominal closure with 3L urological irrigation bags, because in most cases, there was massive sepsis leading to the conclusion that primary closure was not advisable. Indicative of the seriousness of these conditions, Apache score averaged 19 (range 10-30). The technique consisted of suturing a double thickness of irrigation bags to each side of the wound, and joining the two bags in the midline with running sutures. Abdominal lavage with large quantities of fluid was performed every other day. This type of closure was used for a mean duration of 15 days. Mean length of hospitalization was 60 days. There were only three deaths (17.6%). No incisional hernia occurred after the iterative laparotomies. Deleting patients with acute pancreatitis would have reduced the death rate to only 7%. A 3L urological irrigation bag costs pound 11.60 (24.40 dollars CAN) while a Marlex mesh costs pound 81.40 (171.00 dollars CAN). We conclude that the usage of 3L urological plastic bags is a simple, safe and efficient method for temporary closure of the abdomen.

Implication of ATP and sodium in arachidonic acid incorporation by placental syncytiotrophoblast brush border and basal plasma membranes in the human.

The human placental syncytiotrophoblast is the main site of exchange of nutrients and minerals between the mother and her fetus. In order to characterize the placental transport of some fatty acids, we studied the incorporation of arachidonic acid, a fetal primordial fatty acid, in purified bipolar syncytiotrophoblast brush border (BBM) and basal plasma membranes (BPM) from human placenta. The basal arachidonic acid incorporation in BBM and BPM was time dependent and reached maximal values of 0.75+/-0.10 and 0.48+/-0.18 pmol/mg protein, respectively, after 2.5 min. The presence of adenosine triphosphate (ATP) (3 m m) increases significantly the maximal incorporation of arachidonic acid by sixfold (4.75+/-0.35 pmol/mg) and ninefold (4.40+/-0.84 pmol/mg) in BBM and BPM, respectively. Moreover, an increase in the arachidonic acid incorporation was also obtained in the presence of sodium where the values achieved 7.68+/-0.98 (10x) and 6.53 pmol/mg (13.6x) for BBM and BPM, respectively. We also showed that the combination of both Na(+)and ATP increases significantly the maximal incorporation of arachidonic acid in BPM to 7.89+/-0.15 pmol/mg protein, while in BBM it did not modify its incorporation (8.18+/-0.25 pmol/mg protein), as compared to the presence of sodium alone. Our results demonstrate that arachidonic acid is incorporated by both placental syncytiotrophoblast membranes, and is ATP and sodium-linked. However, different mechanisms seem to be involved in this fatty acid incorporation through BBM and BPM, since the presence of Na(+)or ATP increased it, while the association of these two elements increased it only in BPM. We also demonstrated by osmolarity experiments that both membranes bind arachidonic acid, potentially involving one or more fatty acids binding proteins.

Altered expression and functions of serotonin 5-HT1A and 5-HT1B receptors in knock-out mice lacking the 5-HT transporter.

By taking up serotonin (5-hydroxytryptamine, 5-HT) released in the extracellular space, the 5-HT transporter (5-HTT) regulates central 5-HT neurotransmission. Possible adaptive changes in 5-HT neurotransmission in knock-out mice that do not express the 5-HT transporter were investigated with special focus on 5-HT1A and 5-HT1B receptors. Specific labelling with radioligands and antibodies, and competitive RT-PCR, showed that 5-HT1A receptor protein and mRNA levels were significantly decreased in the dorsal raphe nucleus (DRN), increased in the hippocampus and unchanged in other forebrain areas of 5-HTT-/- vs. 5-HTT+/+ mice. Such regional differences also concerned 5-HT1B receptors because a decrease in their density was found in the substantia nigra (-30%) but not the globus pallidus of mutant mice. Intermediate changes were noted in 5-HTT+/- mice compared with 5-HTT+/+ and 5-HTT-/- animals. Quantification of [35S]GTP-gamma-S binding evoked by potent 5-HT1 receptor agonists confirmed such changes as a decrease in this parameter was noted in the DRN (-66%) and the substantia nigra (-30%) but not other brain areas in 5-HTT-/- vs. 5-HTT+/+ mice. As expected from actions mediated by functional 5-HT1A and 5-HT1B autoreceptors, a decrease in brain 5-HT turnover rate after i.p. administration of ipsapirone (a 5-HT1A agonist), and an increased 5-HT outflow in the substantia nigra upon local application of GR 127935 (a 5-HT1B/1D antagonist) were observed in 5-HTT+/+ mice. Such effects were not detected in 5-HTT-/- mice, further confirming the occurrence of marked alterations of 5-HT1A and 5-HT1B autoreceptors in these animals.

Scintimammography with 11beta-methoxy-(17alpha,20Z)-[123I]iodovinylestrad iol: a complementary role to 99mTc-methoxyisobutyl isonitrile in the characterization of breast tumors.

UNLABELLED: The aim of this study was to investigate a possible relationship between 99mTc-methoxyisobutyl isonitrile (MIBI) uptake and the estrogen receptor (ER) status of breast tumors as determined by 11beta-methoxy-(17alpha,20Z)-[123I]iodovinylestradi ol (MIVE) scintimammography. METHODS: Thirteen patients referred for MIVE scintimammography after abnormal mammography or finding of a suspect mass on physical examination were injected intravenously with MIVE. Planar images of the breasts and axillary region were taken with both radiopharmaceuticals and compared with pathologic examination of the tumor tissue and in vitro ER quantification. RESULTS: The presence of cancerous tissue, as indicated by MIBI uptake, is a prerequisite for the accumulation of MIVE by the breast tumors. There was no statistically significant correlation between the MIBI and MIVE tumor uptake ratios. However, the latter correlate well with the presence of ER, as determined by an in vitro assay. CONCLUSION: MIVE scans add unique information concerning the tumor ER status in breast cancer patients, which could contribute to a better characterization of the tumor and aid in the selection of the most appropriate treatment protocol.

Adaptive changes of serotonin 5-HT2A receptors in mice lacking the serotonin transporter.

The serotonin transporter (5-HTT) plays a key-role in the control of serotoninergic neurotransmission and is the target of some antidepressants. Possible adaptive changes in brain 5-HT2A receptors were investigated in knock-out mice that do not express the 5-HTT. Autoradiographic labeling of these receptors by the selective antagonist [3H]MDL 100,907 and saturation experiments with cortical membranes revealed: (1) a new localization of these receptors in the external field of striatum (possibly in striosomes); (2) regional variations in adaptive changes in the density of 5-HT2A receptors in 5-HT(-/-) mutants (-30-40% in the claustrum, cerebral cortex and lateral striatum; no significant change in the striatum core) as compared to wild-type mice.

[Abnormal response of growth hormone to oral glucose tolerance test in obesity]. / Réponse anormale de l'hormone de croissance au cours de l'hyperglycémie provoquée orale chez le sujet obèse.

In obesity, it is well known that basal growth hormone (GH) levels can be suppressed and they may show an impaired response to various stimuli like hypoglycemia, stress, and GHRH. However, the inhibitory effect of hyperglycemia on GH in this condition has not been well studied. We analyzed the GH response to an oral glucose tolerance test (OGTT) in 25 unselected patients with morbid obesity who were not diabetic, glucose intolerant or affected by renal or hepatic disease. Ten (40%) of the 25 subjects had an abnormal response of GH to the OGTT, expressed by a lack of suppression of GH levels below 2 micrograms/L within 60 minutes of glucose administration. Three subjects even had a paradoxal increase of GH levels of more than 50% of the basal level. There was no significant difference between these subjects regarding their age, BMI and, serum levels of glucose, insulin, C peptide, or insulin/glucose ratio. After weight loss, three of four patients normalized their GH response. Thus, we conclude that patients with morbid obesity frequently have an abnormal response of GH to OGTT (40% vs 4-8% in normal subjects). This finding must be taken into consideration when interpreting GH levels in these patients. A normalization of this response can be expected after weight loss.

NADH-dependent tiglyl-CoA reduction in disrupted mitochondria of Ascaris suum.

The incubation of 2-methylcrotonyl-CoA with either succinate or NADH and disrupted Ascaris suum mitochondria results in substantial 2-methylbutyrate formation. Both membrane-bound and soluble components are required and the NADH-dependent reduction is rotenone sensitive, suggesting the involvement of the electron-transport chain. Rat liver mitochondria, incubated under similar conditions, did not catalyze 2-methylbutyrate formation. However, the substitution of A. suum mitochondrial membranes for rat liver membranes stimulated 2-methylbutyrate formation, emphasizing the differences in electron-transport in these two organelles.

Juvenile carcinoma of the breast.

A case of secretory or juvenile carcinoma of the breast is reported in a 16 year old girl. A wide local excision was performed and no recurrence or lymph node metastases were detected at follow-up. This uncommon variety of breast tumor can also occur in adults. Most reports stress the low degree of malignancy with a slow rate of growth and a minimal risk of metastatic spread. Because of the limited number of cases reported, the initial treatment of choice is debatable. Consequently we suggest that the treatment of such a lesion should be individualized.

Angiosarcoma of the breast.

The authors report a case of angiosarcoma of the breast. The patient, a 44-year-old woman, remains free of disease 7 years after biopsy and 6 years after a simple mastectomy. The authors emphasize the benign appearance of the tumour and the importance of early detection and adequate surgical treatment.