Ang II acutely stimulates Na,K-pump in cells from proximal tubules by increasing its phosphorylation at S938 via a PI3K/AKT pathway.

Angiotensin II (Ang II)-dependent stimulation of the AT1 receptor in proximal tubules increases sodium reabsorption and blood pressure. Reabsorption is driven by the Na,K-pump that is acutely stimulated by Ang II, which requires phosphorylation of serine-938 (S938). This site is present in humans and only known to phosphorylated by PKA. Yet, activation of AT1 decreases cAMP required to activate PKA and inhibiting PKA does not block Ang II-dependent phosphorylation of S938. We tested the hypothesis that Ang II-dependent activation is mediated via increased phosphorylation at S938 through a PI3K/AKT-dependent pathway. Experiments were conducted using opossum kidney cells, a proximal tubule cell line, stably co-expressing the AT1 receptor and either the wild-type (α-1.wild-type) or an alanine substituted (α-1.S938A) form of rat kidney Na,K-pump. A 5-min exposure to 10 pM Ang II significantly activated Na,K-pump activity (56%) measured as short-circuit current across polarized α-1.wild-type cells. Wortmannin, at a concentration that selectively inhibits PI3K, blocked that Ang II-dependent activation. Ang II did not stimulate Na,K-pump activity in α-1.S938A cells. Ang II at 10 and 100 pM increased phosphorylation at S938 in α-1.wild-type cells measured in whole cell lysates. The increase was inhibited by wortmannin plus H-89, an inhibitor of PKA, not by either alone. Ang II activated AKT inhibited by wortmannin, not H-89. These data support our hypothesis and show that Ang II-dependent phosphorylation at S938 stimulates Na,K-pump activity and transcellular sodium transport.

Prurigo Pigmentosa Following a Keto Diet and Bariatric Surgery.

Prurigo pigmentosa (PP) is a rare pruritic condition with idiopathic etiology that affects mostly females. It most commonly presents as a rash on the neck and trunk. We report the occurrence of PP in a young woman on two separate occasions; her first episode was following a ketogenic diet and second after undergoing a laparoscopic gastric sleeve surgery. This presents as a unique case because, to our knowledge, PP has only been reported in a small number of cases in the Western world. This presentation could be suggestive of a stronger relationship between PP and the metabolic state of the body. It also outlines the effectiveness of treatment options currently in use for treating PP.

Improving Symptoms of Peripheral Artery Disease With Hirudotherapy.

Peripheral artery disease (PAD) is a significant cause of morbidity and mortality in the world. Critical limb ischemia is a complication of PAD that leads to severe pain at rest, numbness, and absent or diminished pulses in the legs or feet. Revascularization with surgery or endovascular intervention is required to re-establish blood flow to the affected areas. Failure to respond to medical and/or surgical treatment can lead to amputations. The decision to amputate one's limb can be very challenging. Here, we report a patient with critical limb ischemia who refused a below-the-knee amputation and self-treated with medicinal leech therapy, or hirudotherapy. His symptoms including his pain, burning, and numbness improved significantly following six months of therapy.

Merkel Cell Carcinoma in the Setting of Chronic Lymphocytic Leukemia and Diffuse Large B-Cell Lymphoma.

Merkel cell carcinoma (MCC) is a rare, rapidly growing, and highly malignant cutaneous tumor that typically presents in elderly males as an erythematous or violaceous plaque or nodule in sun-exposed areas. Risk factors include long-term ultraviolet (UV) exposure, Merkel cell polyomavirus (MCV) infection, immunosuppression, and lymphoproliferative disorders such as chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Given the aggressive nature of this tumor, patients may present with nodal and distal metastasis. Locoregional disease can be managed with definitive radiotherapy or surgery with or without adjuvant radiotherapy, depending on the case. Disseminated disease, on the other hand, often requires a multidisciplinary tumor board consultation to individually tailor the treatment. Possible treatments include systemic therapy with chemotherapy or immunotherapy, radiotherapy, and surgery. Here we report a case of a patient with a medical history significant for chronic lymphocytic leukemia and diffuse large B-cell lymphoma who presented with a rapidly growing lesion that contained neighboring MCC and CLL/SLL on biopsy. Management included immunotherapy with pembrolizumab and radiotherapy to limit the tumor's growth and spread. To the best of our knowledge, the coexistence of all three malignancies in a person is rare and has not been reported previously.