Physiology and pathophysiology of the vasopressin-regulated renal water reabsorption

To prevent dehydration, terrestrial animals and humans have developed a sensitive and versatile system to maintain their water homeostasis. In states of hypernatremia or hypovolemia, the antidiuretic hormone vasopressin (AVP) is released from the pituitary and binds its type-2 receptor in renal principal cells. This triggers an intracellular cAMP signaling cascade, which phosphorylates aquaporin-2 (AQP2) and targets the channel to the apical plasma membrane. Driven by an osmotic gradient, pro-urinary water then passes the membrane through AQP2 and leaves the cell on the basolateral side via AQP3 and AQP4 water channels. When water homeostasis is restored, AVP levels decline, and AQP2 is internalized from the plasma membrane, leaving the plasma membrane watertight again. The action of AVP is counterbalanced by several hormones like prostaglandin E2, bradykinin, dopamine, endothelin-1, acetylcholine, epidermal growth factor, and purines. Moreover, AQP2 is strongly involved in the pathophysiology of disorders characterized by renal concentrating defects, as well as conditions associated with severe water retention. This review focuses on our recent increase in understanding of the molecular mechanisms underlying AVP-regulated renal water transport in both health and disease

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta

Câncer do reto médio: avaliação do procedimento cirúrgico

A conduta no tratamento cirúrgico do câncer do reto médio é ainda controversa. Vários procedimentos cirúrgicos foram avaliados, retrospectivamente, em noventa doentes operados durante o período de fevereiro de 1990 a junho de 1997. Deste total, 43 (47,7%) doentes eram do sexo feminino e 47 (52,3%) do masculino. A idade variou entre 20 e 90 anos, com média de 60,2 anos. Os principais sintomas e sinais foram puxo e tenesmo, hematoquesia e emagrecimento. O tempo decorrido desde o início dos sintomas até o diagnóstico variou de dois a 24 meses, com média de 7,5 meses. A amputação abdômino-perineal do reto foi realizada em 17 doentes (18,8%) e a complicação mais freqüente foi a deiscência da ferida perineal, em 47% dos casos. Um doente (1,1 %) foi submetido a proctocolectomia total, evoluindo sem intercorrências. A operação de Hartmann foi feita em 26 doentes (28,8%), ocorrendo 7,6% de morbidade e 7,6% de mortalidade, em virtude de complicações clínicas. Em 26 doentes (28,8%), foi realizada ressecção anterior seguida de anastomose. Em dez (11,1%), foi realizada anastomose manual e não houve complicações. Nos outros 16 (17,7%) foi feita anastomose mecânica, havendo três deiscências e um óbito, relacionado a complicações clínicas. Em oito doentes (8,8%), foi realizada ressecção com abaixamento coloanal, ocorrendo 50% de complicações, devido à necrose e à retração do cólon abaixado. Houve apenas um óbito relacionado à complicação cirúrgica. Em 12 doentes (13,3%) não foi efetuada a ressecção do tumor, em decorrência de precárias condições clínicas dos mesmos e falta de critérios de ressecabilidade da lesão. Concluímos que o procedimento cirúrgico adequado no tratamento do câncer do reto médio depende de estadiamento criterioso, considerando o grau de diferenciação celular, a presença de metástase, a condição local do tumor, a situação clínica do doente e a experiência da equipe cirúrgica