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Currarino triad with dual pathology in the presacral mass: report of a case.

PURPOSE: Currarino triad, which comprises anorectal stenosis, anterior sacral defect, and a presacral mass, is an uncommon cause of constipation in children and adults. The presacral mass in this triad is most often caused by an anterior sacral meningocele, a teratoma, or an enterogenous cyst, but rarely may be caused by dual pathology. A neonate with Currarino triad and dual pathology in the presacral mass is described in this report. METHOD: A male Chinese neonate, who presented with abdominal distention and constipation on the second day of life, was found to have features of Currarino triad. Colostomy was done in the neonatal period, and the presacral mass was excised by posterior sagittal perineal approach at the age of six months. RESULTS: The excised presacral mass consisted of an anterior meningocele and a teratoma. The patient continued to have constipation during follow-up and required anorectoplasty to correct residual anorectal stenosis. At the time of this report the patient was three years old and growing normally with normal anorectal function. DISCUSSION: Of a total of about 200 cases of complete Currarino triad found in the literature, in only 22 patients did the presacral mass contain both meningocele and teratoma. The features of these 22 patients and the current views on the surgical management of Currarino triad are discussed.

Abnormalities, Multiple↗

Deficiency of triad formation in developing skeletal muscle cells lacking junctophilin type 1.

Junctophilins (JP-1, JP-2, and JP-3) are transmembrane proteins expressed in the junctional membrane complexes in excitable cells. Both JP-1 and JP-2 are co-expressed in the triads of skeletal muscle, but only JP-2 is expressed in cardiac muscle. We analyzed the roles played by JP-1 and JP-2 in triad formation in skeletal muscle by comparing developing skeletal muscles in wild-type and JP-1-knockout (KO) mice (both before and after birth). In the skeletal muscles of embryos, most of the couplings between sarcoplasmic reticulum (SR) and transverse tubule (T-tubule) were diads, with triads being very scarce. The number of triads increased markedly after birth in wild-type mice. However, there was no increase in the number of triads in the neonates of JP-1-KO mice, and they died within 1 day after birth. JP-2 expression was constant before and after birth, while expression of JP-1 increased with birth. Quantitative and morphological differences were not seen between wild-type and JP-1-KO mice in the formation of diads in the period just before the JP-1-KO mice died. The SR swelled and developed large vacuoles in skeletal muscle cells just before the JP-1-KO mice died. The present results strongly suggest that JP-1 and JP-2 play important roles in the formation of triads and diads, respectively, during the development of skeletal muscle in mouse.

Animals↗

Mutagenesis of some positive and negative residues occurring in repeat triad residues in the ADP/ATP carrier from yeast.

In AAC2 from Saccharomyces cerevisiae, nine additional charged residues (six positive, three negative) were neutralized by mutagenesis following the previous mutation of six arginines. Oxidative phosphorylation (OxPhos) in cells and mitochondria, the expression level of AAC protein, and the various transport modes of AAC in the reconstituted system were measured. Mutations are: within the first helix at K38A which is exclusive for AAC; K48A, and R152A, part of a positive triad occurring in the matrix portion of each repeat; two matrix lysines, K179M and K182I, and the negative triad helix-terminating residues, E45G, D149S, D249S. Cellular ATP synthesis (OxPhos) is nearly completely inhibited in K48A, R152A, D149S, and D249S, but still amounts to 10% in K38A and between 30% and 90% in the gly+ mutants K179M, K179I + K182I, and E45G. Comparison of the AAC content measured by ELISA and the binding of [3H]CAT and [3H]BKA reveals discrepancies in K48A, D149S, and D249S mitochondria, which provide evidence that these mutations largely abolish inhibitor binding. Also these mitochondria have undetectable OxPhos. Differently in K38A, CAT and BKA binding are retained at high AAC levels but OxPhos is very low. This reveals a special functional role of K38, different from the more structural role of R152, K48, D149, and D249. Transport activity was measured with reconstituted AAC. The electroneutral ADP/ADP exchange of gly- mutants is largely or fully suppressed in K48A, D149S, and D249S. K38A and R152A are still active at 18% and 30% of wt. The other three exchange modes, ATP/ADP, ADP/ATP, and ATP/ATP, are nearly suppressed in all gly- mutants but remain high in gly+ mutants. ATP-linked modes are higher than the ADP/ADP mode in gly+ but lower in gly- mutants, resulting in an exchange mode inversion (EMI). In the competition for AAC2 transport capacity, the weak ATP exporting modes are suppressed by the much stronger unproductive ADP/ADP mode causing inhibition of OxPhos. Together with previous results all members of three charge triads are now mutagenized, revealing drastic functional rotatory asymmetries within the three repeat domains. In the intrahelical arginine triad the third (R294A), in the positive matrix triad the second (R152A), and in the helix-terminating negative triad the first (E45G) still show high activity.

Adenosine Triphosphate↗

Electron donor-acceptor dyads and triads based on tris(bipyridine)ruthenium(II) and benzoquinone: synthesis, characterization, and photoinduced electron transfer reactions.

Two electron donor-acceptor triads based on a benzoquinone acceptor linked to a light absorbing [Ru(bpy)(3)](2+) complex have been synthesized. In triad 6 (denoted Ru(II)-BQ-Co(III)), a [Co(bpy)(3)](3+) complex, a potential secondary acceptor, was linked to the quinone. In the other triad, 8 (denoted PTZ-Ru(II)-BQ), a phenothiazine donor was linked to the ruthenium moiety. The corresponding dyads Ru(II)-BQ (4) and PTZ-Ru(II) (9) were prepared for comparison. Upon light excitation in the visible band of the ruthenium moiety, electron transfer to the quinone occurred with a rate constant k(f) = 5 x 10(9) s(-)(1) (tau(f) = 200 ps) in all the quinone containing complexes. Recombination to the ground state followed, with a rate constant k(b) approximately 4.5 x 10(8) s(-)(1) (tau(b) approximately 2.2 ns), for both Ru(II)-BQ and Ru(II)-BQ-Co(III) with no indication of a charge shift to generate the reduced Co(II) moiety. In the PTZ-Ru(II)-BQ triad, however, the initial charge separation was followed by a rapid (k > 5 x 10(9) s(-)(1)) electron transfer from the phenothiazine moiety to give the fairly long-lived PTZ(*)(+)-Ru(II)-BQ(*)(-) state (tau = 80 ns) in unusually high yield for a [Ru(bpy)(3)](2+)-based triad (> 90%), that lies at DeltaG degrees = 1.32 eV relative to the ground state. Unfortunately, this triad turned out to be rather photolabile. Interestingly, coupling between the oxidized PTZ(*)(+) and the BQ(*)(-) moieties seemed to occur. This discouraged further extension to incorporate more redox active units. Finally, in the dyad PTZ-Ru(II) a reversible, near isoergonic electron transfer was observed on excitation. Thus, a quasiequilibrium was established with an observed time constant of 7 ns, with ca. 82% of the population in the PTZ-Ru(II) state and 18% in the PTZ(*)(+)-Ru(II)(bpy(*)(-)) state. These states decayed in parallel with an observed lifetime of 90 ns. The initial electron transfer to form the PTZ(*)(+)-Ru(II)(bpy(*)(-)) state was thus faster than what would have been inferred from the Ru(II) emission decay (tau = 90 ns). This result suggests that reports for related PTZ-Ru(II) and PTZ-Ru(II)-acceptor complexes in the literature might need to be reconsidered.

Journal Article↗

Modulating charge separation and charge recombination dynamics in porphyrin-fullerene linked dyads and triads: Marcus-normal versus inverted region.

Photoinduced charge separation (CS) and charge recombination (CR) processes have been examined in various porphyrin-fullerene linked systems (i.e., dyads and triads) by means of time-resolved transient absorption spectroscopy and fluorescence lifetime measurements. The investigated compounds comprise a homologous series of rigidly linked, linear donor-acceptor arrays with different donor-acceptor separations and diversified donor strength: freebase porphyrin-C60 dyad (H2P-C60), zincporphyrin-C60 dyad (ZnP-C60), ferrocene-zincporphyrin-C60 triad (Fc-ZnP-C60), ferrocene-freebase porphyrin-C60 triad (Fc-H2P-C60), and zincporphyrin-freebase porphyrin-C60 triad (ZnP-H2P-C60). Most importantly, the lowest lying charge-separated state of all the investigated systems, namely, that of ferrocenium ion (Fc+) and the C60 radical anion (C60.-) pair in the Fc-ZnP-C60 triad, has been generated with the highest quantum yields (close to unity) and reveals a lifetime as long as 16 micros. Determination of CS and CR rate constants, together with the one-electron redox potentials of the donor and acceptor moieties in different solvents, has allowed us to examine the driving force dependence (-DeltaG0ET) of the electron-transfer rate constants (kET). Hereby, the semilogarithmic plots (i.e., log kET versus -DeltaG0ET) lead to the evaluation of the reorganization energy (lambda) and the electronic coupling matrix element (V) in light of the Marcus theory of electron-transfer reactions: lambda = 0.66 eV and V = 3.9 cm(-1) for ZnP-C60 dyad and lambda = 1.09 eV and V = 0.019 cm(-1) for Fc-ZnP-C60, Fc-H2P-C60, and ZnP-H2P-C60 triads. Interestingly, the Marcus plot in Fc-ZnP-C60, Fc-H2P-C60, and ZnP-H2P-C60 has provided clear evidence for intramolecular CR located in both the normal and inverted regions of the Marcus parabola. The coefficient for the distance dependence of V (damping factor: betaCR = 0.58 A(-1) is deduced which depends primarily on the nature of the bridging molecule.

Porphyrins↗

RANTES, eotaxin and eotaxin-2 expression and production in patients with aspirin triad.

BACKGROUND: Polyposis, asthma, aspirin-intolerance and aspirin-triad are mostly accompanied with eosinophilia of mucosal airways. Chemotactic cytokines, the CC-chemokines regulated on activation, normal T-cell expressed (RANTES), eotaxin, and eotaxin-2 activate and attract eosinophilic leukocytes to the site of inflammation. This points to the implication of CC-chemokines in eosinophilia of nasal tissue of these diseases. METHODS: Therefore, nasal polypous tissue specimens of patients suffering from chronic nasal polypous sinusitis (NP), intrinsic asthma (ATA), aspirin-intolerance (AINA), and aspirin-triad (TRIAD) were investigated. The amount of mRNA and protein of CC-chemokines was analyzed using semi-quantitative reverse transcriptase polymerase chain reaction and chemokine-specific enzyme-immuno-assays. The patterns of CC-chemokines were compared. RESULTS: The mRNA-expression as well as protein synthesis of CC-chemokines was quantified in all tissues investigated. The expression of RANTES-mRNA in NP, ATA, AINA, and TRIAD (averaging 148-324% D-glyceraldehyde-3-phosphate dehydrogenase) and protein synthesis (0.13-0.15 ng/mg tissue weight) did not differ significantly. But the protein synthesis of eotaxin- and eotaxin-2-mRNA was significantly (P < 0.05) higher in TRIAD (3.3 pg/mg and 3.4 ng/mg tissue weight) (4 ng/mg tissue weight), than in NP, ATA, or AINA (1.8 pg/mg and 2.1 ng/mg, 2.1 pg/mg and 1.6 ng/mg, or 1.7 pg/mg and 2.2 ng/mg tissue weight, respectively). CONCLUSION: Patients suffering from TRIAD in association with tissue eosinophilia were characterized by elevated eotaxin and eotaxin-2 mRNA-expression as well as protein-synthesis. This pointed to the implication of eotaxins and RANTES in eosinophilia-associated diseases. Further studies will have to prove, whether the analysis of these chemokines might improve the diagnosis of eosinophilia associated polyposis and initiate the development of new therapeutic strategies.

Adult↗

Bombyx mori single repeat telomeric DNA sequence forms a G-quadruplex capped by base triads.

A combined NMR-molecular dynamics approach has been applied to determine the solution structure of a truncated analogue of the Bombyx mori telomeric d(TTAGG) single repeat sequence in Na+ cation-containing aqueous solution. The two-fold symmetric four-stranded d(TAGG) quadruplex contains two adjacent G(syn).G(syn).G(anti).G(anti) G-tetrads sandwiched between novel (T.A).A triads with individual strands having both a parallel and antiparallel neighbour around the quadruplex. The (T.A).A triad represents the first experimental verification of a base triad alignment which constitutes a key postulate in the recently proposed model of triad-DNA. Further, the (T.A).A triad is generated by positioning an A residue through hydrogen bonding in the minor groove of a Watson-Crick T.A base pair and includes a T-A platform related to an A-A platform recently observed in the structure of the P4-P6 domain of the Tetrahymena self splicing group I ribozyme. The novel architecture of the truncated Bombyx mori quadruplex structure sets the stage for the design and potential identification of additional base tetrads and triads that could participate in pairing alignments of multi-stranded DNA structures during chromosome association and genetic recombination.

Animals↗

Cross-linking analysis of the ryanodine receptor and alpha1-dihydropyridine receptor in rabbit skeletal muscle triads.

In mature skeletal muscle, excitation-contraction (EC) coupling is thought to be mediated by direct physical interactions between the transverse tubular, voltage-sensing dihydropyridine receptor (DHPR) and the ryanodine receptor (RyR) Ca2+ release channel of the sarcoplasmic reticulum (SR). Although previous attempts at demonstrating interactions between purified RyR and alpha1-DHPR have failed, the cross-linking analysis shown here indicates low-level complex formation between the SR RyR and the junctional alpha1-DHPR. After cross-linking of membranes highly enriched in triads with dithiobis-succinimidyl propionate, distinct complexes of more than 3000 kDa were detected. This agrees with numerous physiological and electron-microscopic findings, as well as co-immunoprecipitation experiments with triad receptors and receptor domain-binding studies. However, a distinct overlap of immunoreactivity between receptors was not observed in crude microsomal preparations, indicating that the triad complex is probably of low abundance. Disulphide-bonded, high-molecular-mass clusters of triadin, the junctional protein proposed to mediate interactions in triads, were confirmed to be linked to the RyR. Calsequestrin and the SR Ca2+-ATPase were not found in cross-linked complexes of the RyR and alpha1-DHPR. Thus, whereas recent studies indicate that the two receptors exhibit temporal differences in their developmental inductions and that receptor interactions are not essential for the formation and maintenance of triads, this study supports the signal transduction hypothesis of direct physical interactions between triad receptors in adult skeletal muscle.

Animals↗

Cooperation of two-domain Ca(2+) channel fragments in triad targeting and restoration of excitation- contraction coupling in skeletal muscle.

The specific incorporation of the skeletal muscle voltage-dependent Ca(2+) channel in the triad is a prerequisite of normal excitation-contraction (EC) coupling. Sequences involved in membrane expression and in targeting of Ca(2+) channels into skeletal muscle triads have been described in different regions of the alpha(1S) subunit. Here we studied the targeting properties of two-domain alpha(1S) fragments, green fluorescent protein (GFP)-I x II (1-670) and III x IV (691-1873) expressed alone or in combination in dysgenic (alpha(1S)-null) myotubes. Immunofluorescence analysis showed that GFP-I x II or III x IV expressed separately were not targeted into triads. In contrast, on coexpression the two alpha(1S) fragments were colocalized with one another and with the ryanodine receptor in the triads. Coexpression of GFP-I x II and III x IV also fully restored Ca(2+) currents and depolarization-induced Ca(2+) transients, despite the severed connection between the two channel halves and the absence of amino acids 671-690 from either alpha(1S) fragment. Thus, triad targeting, like the rescue of function, requires the cooperation and coassembly of the two complementary channel fragments. Transferring the C terminus of alpha(1S) to the N-terminal two-domain fragment (GFP-I x II x tail), or transferring the I-II connecting loop containing the beta interaction domain to the C-terminal fragment (III x IV x beta in) did not improve the targeting properties of the individually expressed two-domain channel fragments. Thus, the cooperation of GFP-I.II and III.IV in targeting cannot be explained solely by a sequential action of the beta subunit by means of the I-II loop in releasing the channel from the sarcoplasmic reticulum and of the C terminus in triad targeting.

Animals↗

A transverse tubule NADPH oxidase activity stimulates calcium release from isolated triads via ryanodine receptor type 1 S -glutathionylation.

We report here the presence of an NADPH oxidase (NOX) activity both in intact and in isolated transverse tubules and in triads isolated from mammalian skeletal muscle, as established by immunochemical, enzymatic, and pharmacological criteria. Immunohistochemical determinations with NOX antibodies showed that the gp91(phox) membrane subunit and the cytoplasmic regulatory p47(phox) subunit co-localized in transverse tubules of adult mice fibers with the alpha1s subunit of dihydropyridine receptors. Western blot analysis revealed that isolated triads contained the integral membrane subunits gp91(phox) and p22(phox), which were markedly enriched in isolated transverse tubules but absent from junctional sarcoplasmic reticulum vesicles. Isolated triads and transverse tubules, but not junctional sarcoplasmic reticulum, also contained varying amounts of the cytoplasmic NOX regulatory subunits p47(phox) and p67(phox). NADPH or NADH elicited superoxide anion and hydrogen peroxide generation by isolated triads; both activities were inhibited by NOX inhibitors but not by rotenone. NADH diminished the total thiol content of triads by one-third; catalase or apocynin, a NOX inhibitor, prevented this effect. NADPH enhanced the activity of ryanodine receptor type 1 (RyR1) in triads, measured through [3H]ryanodine binding and calcium release kinetics, and increased significantly RyR1 S-glutathionylation over basal levels. Preincubation with reducing agents or NOX inhibitors abolished the enhancement of RyR1 activity produced by NADPH and prevented NADPH-induced RyR1 S-glutathionylation. We propose that reactive oxygen species generated by the transverse tubule NOX activate via redox modification the neighboring RyR1 Ca2+ release channels. Possible implications of this putative mechanism for skeletal muscle function are discussed.

Animals↗

Purification of morphologically intact triad structures from skeletal muscle.

A procedure has been devised for isolation of triads (t-tubule/sarcoplasmic reticulum (SR) junctional complexes) from rabbit skeletal muscle. The procedure consists of preparation of a heavy microsomal fraction followed by two sequential 90-min sucrose gradient centrifugations to enrich the triads. A pyrophosphate/phosphate/magnesium buffer system was introduced to decrease aggregation in order to achieve effective separation. The preparation time is 12 h. Some differences between purified triads isolated by two variants of this method are noted. The purity of the triad fractions has been estimated by particle counting to be in the vicinity of 50%. There is good retention of morphology and Ca++-loading activity and enrichment in Na+,K+-ATPase and adenylate cyclase. The triads are practically devoid of contractile elements, mitochondria, and free plasmalemma, and low in content of light SR. The method for obtaining enriched triads is reproducible, and sufficient yields are obtained for structural, biochemical, and functional characterization.

Adenylyl Cyclases↗

Genetic association analysis using data from triads and unrelated subjects.

The selection of an appropriate control sample for use in association mapping requires serious deliberation. Unrelated controls are generally easy to collect, but the resulting analyses are susceptible to spurious association arising from population stratification. Parental controls are popular, since triads comprising a case and two parents can be used in analyses that are robust to this stratification. However, parental controls are often expensive and difficult to collect. In some situations, studies may have both parental and unrelated controls available for analysis. For example, a candidate-gene study may analyze triads but may have an additional sample of unrelated controls for examination of background linkage disequilibrium in genomic regions. Also, studies may collect a sample of triads to confirm results initially found using a traditional case-control study. Initial association studies also may collect each type of control, to provide insurance against the weaknesses of the other type. In these situations, resulting samples will consist of some triads, some unrelated controls, and, possibly, some unrelated cases. Rather than analyze the triads and unrelated subjects separately, we present a likelihood-based approach for combining their information in a single combined association analysis. Our approach allows for joint analysis of data from both triad and case-control study designs. Simulations indicate that our proposed approach is more powerful than association tests that are based on each separate sample. Our approach also allows for flexible modeling and estimation of allele effects, as well as for missing parental data. We illustrate the usefulness of our approach using SNP data from a candidate-gene study of psoriasis.

Algorithms↗

Assessing maternal genetic associations: a comparison of the log-linear approach to case-parent triad data and a case-control approach.

BACKGROUND: In utero exposures, including maternal phenotypes, are potential risk factors for both early-onset and adult-onset diseases. Two alternative study designs use maternal genotypes at polymorphic loci as biomarkers of an offspring's in utero exposure: (1) a traditional case-control study with logistic regression analysis, in which cases, controls, and mothers of both types of subjects are genotyped; and (2) a case-parent triad study with log-linear analysis, in which cases and both parents are genotyped. METHODS: We used computer simulations to compare the operating characteristics of the log-linear approach to case-parent triad data and the case-control approach for assessing relative risks (RRs) associated with maternal genotypes. RESULTS: For high-risk allele frequencies (chromosomal prevalence; f) between 0.20 and 0.75, both methods allowed for valid, unbiased estimates of maternal RRs. The case-parent triad approach, however, had 43% greater power, on average, than the case-control approach with an equal number of genotypes, and 13% greater power with an equal number of cases. For example, under dominant inheritance, to detect 2-fold maternal RRs with 200 (or 150) cases when allele prevalence is between 0.15 and 0.40, the case-parent triad and equal-genotype case-control designs had, on average, 87% and 62% power, respectively. As f approached 0 or 1, the power of both methods decreased sharply. DISCUSSION: The greater efficiency of case-parent triads may be due to the inclusion of paternal genotype information, which allows for independent tests of disease association with maternal or offspring genotypes. These results highlight one potential advantage of case-parent triad data in assessing maternal genetics as risk factors for offspring disease. We discuss these findings and other considerations between the 2 methodological approaches.

Case-Control Studies↗

Altered E-C coupling in triads isolated from malignant hyperthermia-susceptible porcine muscle.

Triad vesicles were isolated from normal (N) and homozygous malignant hyperthermia-susceptible (MHS) porcine skeletal muscle, and two types of sarcoplasmic reticulum Ca2+ release were investigated: 1) polylysine-induced Ca2+ release (direct stimulation of the junctional foot protein), and 2) depolarization-induced Ca2+ release (stimulation of the junctional foot protein via the dihydropyridine receptor). At submaximal concentrations of polylysine, the rates of induced Ca2+ release from the MHS triads were greater than from normal triads. The T tubules of polarized triads were depolarized by the K(+)-to-Na+ ionic replacement protocol. Higher grades of T-tubule depolarization resulted in higher rates of Ca2+ release from both MHS and normal triads but, when compared at a given grade of T-tubule depolarization, the release rate was always greater from the MHS than from normal triads. Thus the activity of the SR Ca2+ release channel is always higher in MHS than in normal muscle at a given submaximal dose of release trigger. This difference is observed when the channel is stimulated directly by polylysine or indirectly via a depolarization-induced activation of the T-tubule dihydropyridine receptor.

Animals↗

Comparison of Ca2+ loading and retention in isolated skeletal muscle triads and terminal cisternae.

Ca2+ loading and retention were examined in isolated skeletal muscle triads and terminal cisternae to determine 1) whether excessive loading altered the response of triads to depolarization-induced Ca2+ release and 2) whether these vesicles were similar in their ability to load and retain Ca2+. A mixture of triads and terminal cisternae was loaded with variable amounts of Ca2+ and then subjected to maximal depolarization. Ca2+ release was monitored by changes in extravesicular fura 2 fluorescence using 340/380-nm excitation and 510-nm emission wavelengths. The amount of Ca2+ released from triads due to maximal depolarization increases with increasing Ca2+ loads until a maximal response is obtained, indicating triad saturation. At pH 7, triadic vesicles preferentially loaded and retained Ca2+ at low Ca2+ loads, but, with increasing loads, nontriadic vesicles began to retain Ca2+. At pH 6.5, which should close all open uncoupled ryanodine receptors, triadic and isolated terminal cisternae vesicles loaded and retained Ca2+ in a similar manner. A population of triads, which have some uncoupled ryanodine receptors, did not retain their loaded Ca2+ at pH 7.0 but did retain Ca2+ at pH 6.5; this resulted in a doubling of the amount of Ca2+ released on maximal depolarization after loading at pH 6.5.

Animals↗

The female athlete triad: an emerging role for physical therapy.

Over the last thirty years, participation by girls and women in organized athletics has increased dramatically. This presents unique challenges in the area of sports medicine, orthopaedics, and pediatrics. While the benefits of participation in sports and exercise vastly outweigh the risks of permanent injury, an evolving concern is the number of stress fractures in active women. The female athlete triad ("triad") describes the coexistence of 3 distinct medical conditions that may occur in athletic girls and women. Originally, the triad included eating disorders, amenorrhea, and osteoporosis. Presently, it includes eating disorders/disordered eating behavior, amenorrhea/oligomenorrhea, and decreased bone mineral density (osteoporosis and osteopenia). Briefly, when coupled with inadequate nutrition, the high caloric expenditure of exercise training resultsin a sustained negative caloric balance or low energy availability, which is exquisitely sensed by the hypothalamus, initiating a complex neuroendocrine adaptive cascade. This cascade is associated with changes in the hypothalamic-pituitary-ovarian axis, such that estrogen levels are decreased, resulting in reproductive dysfunction that may include amenorrhea, oligomenorrhea, or anovulation. Low estrogen in otherwise young healthy women, like menopause, is associated with decreased bone mineral density and increased risk of fractures. The triad is not an inevitable consequence of participation in sports or physical activity at any level, however, exercise may contribute to the disruption of caloric balance. The triad is a complex disorder that requires intervention by a multidisciplinary team. Physical therapists bring a unique expertise to the team. The present review summarizes each component of the triad, component linkage, and the role of physical therapy in prevention, assessment, and intervention.

Adolescent↗

Health care triads and dementia care: integrative framework and future directions.

Physicians are usually the first contact in the health care system for persons with dementia and their family caregivers. This paper provides a synopsis of research findings and knowledge gaps regarding interactions among these participants in the health care triad--primary care physicians, family caregivers, and persons with dementia. Research traditions that inform knowledge about health care triads and dementia care include: older patient-physician relationships; the stress-coping social-support health model that dominates family caregiver research; the social learning-self-efficacy model; and literature on the quality of medical care. An integrative framework is presented to illustrate how the quality of interaction in dementia care encounters may be influenced by specific characteristics of members of the health care triad. Domains of dementia care interaction include symptom diagnosis, symptom management, medication management, support service linkage, and emotional support. The integrative framework also links the quality of interaction in these domains with health-related outcomes relevant to each of the health care triad members. Most empirical research in this area has found that family caregivers are dissatisfied with many aspects of physicians' dementia care, but measurement techniques vary widely and little is known about how the quality of physician care is associated with health-related outcomes. Physician surveys have shown that they are least certain about the quality of support service linkage advice they provide. Virtually no research has examined how the person with dementia experiences medical care encounters with physicians and their family members. Much remains to be learned about the longitudinal experience of each member of the health care triad, and how the quality of dementia care encounters changes over the course of the disease process. In this era of rapidly expanding educational and support service interventions for persons with dementia and their family caregivers, as well as computer-based information about dementia care, the influence of these external factors on health care triad interactions and outcomes also remains to be studied.

Aged↗

Comparison of the effects of continuous and intermittent portal triad occlusion (PTO) in rats.

BACKGROUND/AIMS: It has previously been shown that prolonged ischemia of the liver had a mortal course and a method of intermittent occlusion of the hepatic pedicle was defined in order to minimize the damage to the liver. The present experimental study aimed to compare the effects of continuous and intermittent occlusion of the hepatic pedicle on the liver by measuring serum lactate, serum MDA malondialdehyde and glutathione levels and by evaluating the histologic changes in the liver tissue. METHODOLOGY: Thirty male Wistar albino rats weighing 300 +/- 50 g were divided into three groups of ten animals. Group 1 underwent a sham operation. Animals in group 2 underwent continuous portal triad occlusion (PTO group) for 30 minutes following laparotomy. The remaining ten animals in group 3 underwent intermittent occlusion consisting of 10 minutes of occlusion followed by 10 minutes of reperfusion for a total period of 30 minutes of ischemia. Blood samples were collected at the 1st and 6th postoperative hour for analytical evaluation. After sacrificing the animals, liver samples were obtained for histologic evaluation. RESULTS: The serum lactate levels were significantly higher in both portal triad occlusion groups than in the control at the 1st hour. While lactate levels also increased at the 6th hour in the continuous PTO group, it decreased to the level of control values in the intermittent PTO group. The difference between continuous and intermittent groups was also significant. Despite the unchanged malondialdehyde levels in the control group, malondialdehyde levels were significantly increased at the first and sixth hour in both PTO groups and the levels were also significantly higher than control values. Malondialdehyde levels of intermittent PTO groups at the first and sixth hour were both significantly lower than continue PTO groups. Whole blood glutathione levels were not changed in control groups with time, levels increased significantly in both PTO groups. Glutathione levels were higher than control values in both PTO groups at the first hour. While it turned to its basal value in intermittent PTO groups at the 6th hour, it was still significantly higher in the continuous PTO group. When both PTO groups were compared, glutathione levels were found to be significantly higher in the continuous group both at the first and sixth hour than in the intermittent PTO group. Histopathologic evaluation also showed that there was less damage in the intermittent PTO group than in the continuous PTO group. CONCLUSIONS: Our results show that continuous portal triad occlusion resulted in significant oxidative stress and cell damage as confirmed by increased serum lactate and blood malondialdehyde levels. The blood glutathione levels are increased due to a greater requirement in response to increased oxidative stress induced by portal triad occlusion. It is also confirmed that intermittent portal triad occlusion is safer as it causes less oxidative stress and cell damage so that its use is strongly suggested whenever portal triad occlusion is required.

Animals↗