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Легочная артериальная сенсорная терапия для сердечно-сосудистого амилоидоза у молодого пациента с множественной миеломой.

ОКРУЖАЮЩАЯ СРЕДА: Оценка объема в сердечной амилоидной цепи освещения (AL) амилоидоз сопряжена с трудностями в ходе высокодозированной химиотерапии и аутологической трансплантации стволовых клеток, поскольку клинические результаты и вес тела могут не точно отражать внутриваскулярную загруженность. Резюме дела: A 45-year-old У человека с множественной миеломой, нефротическим синдромом и сердечным амилоидозом во время индуктивной терапии появились заметные колебания объема. Перед SCT был установлен имплантируемый датчик давления легочной артерии (PAP) для направления диуретиков. 22 мм Hg. В пери

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… Management Guideline-directed HF therapy was initiated with spironolactone 25 mg once daily, empagliflozin 10 mg once daily, bisoprolol 2.5 mg once daily, sacubitril/valsartan 24/26 mg twice daily, and bumetanide 1 mg once daily. …

Teclistamab Treatment Followed by Heart Transplantation for Advanced Immunoglobulin Light Chain Amyloid Cardiomyopathy.

BackgroundImmunoglobulin light chain (AL) cardiac amyloidosis carries high mortality, particularly when refractory to standard plasma cell-directed therapy. Deep hematologic remission is essential for heart transplant eligibility.Case summaryA 37-year-old woman with advanced AL cardiomyopathy and refractory plasma cell dyscrasia did not respond to daratumumab-based therapy and could not tolerate venetoclax. She developed rapidly progressive, inotrope-dependent heart failure. Salvage therapy with a B-cell maturation antigen-directed bispecific antibody, teclistamab, induced a rapid, minimal res

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… She was successfully weaned from inotropes, transitioned to oral bumetanide 2 mg daily, and discharged home hemodynamically stable. …

AGA Clinical Practice Update on the Management of Ascites, Volume Overload, and Hyponatremia in Cirrhosis: Expert Review.

DESCRIPTION: The purpose of this American Gastroenterological Association (AGA) Institute Clinical Practice Update (CPU) is to summarize the … gement of volume overload includes escalation or trial of intravenous loop diuretics (furosemide or bumetanide) in bolus (2-3 times per day) or continuous fashion. Cautious escalation can be done every 2-3 days with monitoring of volume status, kidney function, daily weights, and symptoms. BEST PRACTICE ADVICE 13: Advanced strategies in refractory anasarca s …

Neurogenic secretion mediated by the purinergic P2Y1 receptor in guinea-pig small intestine.

We tested the hypothesis that ATP is an enteric neurotransmitter that acts at P2Y1 excitatory purinergic receptors on intestinal secretomotor neurons to evoke neurogenic mucosal secretion in the guinea pig. Ussing chamber methods for studying neurogenic intestinal secretion were used to test the hypothesis. Application of ATP evoked concentration-dependent increases in short circuit current (Isc) indicative of stimulation of electrolyte secretion. MRS2179, a selective P2Y1 purinergic receptor antagonist, suppressed the ATP-evoked responses in a concentration-dependent manner with an IC50 of 0.

Stability of actin cytoskeleton and PKC-delta binding to actin regulate NKCC1 function in airway epithelial cells.

Activation of airway epithelial Na-K-2Cl cotransporter (NKCC)1 requires increased activity of protein kinase C (PKC)-delta, which localizes predominantly to the actin cytoskeleton. Prompted by reports of a role for actin in NKCC1 function, we studied a signaling mechanism linking NKCC1 and PKC. Stabilization of actin polymerization with jasplakinolide increased activity of NKCC1, whereas inhibition of actin polymerization with latrunculin B prevented hormonal activation of NKCC1. Protein-protein interactions among NKCC1, actin, and PKC-delta were verified by Western blot analysis of immunoprec

Nitric oxide transiently converts synaptic inhibition to excitation in retinal amacrine cells.

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABA(A) receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect

Cardiac Amyloidosis Treatment.

Cardiac amyloidosis (CA) is a restrictive cardiomyopathy with a traditionally poor prognosis. Until recently, CA treatment options were limited and consisted predominantly of managing symptoms and disease-related complications. However, the last decade has seen significant advances in disease-modifying therapies, increased awareness of CA, and improved diagnostic methods resulting in earlier diagnoses. In this review, we provide an overview of current and experimental treatments for the predominant types of CA: transthyretin cardiac amyloidosis (ATTR-CA) and immunoglobulin light chain (AL)-med

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… intravenous administration; FDA: Food and Drug Administration; CyBorD: cyclophosphamide-bortezomib-dexamethasone; BMD: bortezomib-melphalan-dexamethasone; ASCT: autologous stem cell transplant TREATMENT CATEGORY | TREATMENT | COMMENTS AND CAVEATS Heart failure | Loop diuretics | Favor bioavailable (bumetanide … Due to frequent gut edema, the more bioavailable loop diuretics, bumetanide and torsemide, are commonly used over furosemide and are sometimes paired with a mineralocorticoid receptor antagonist (MRA) with close monitoring of potassium and renal function. …

[Effect of acupuncture at "Neiguan" (PC6) on behavioral deficits and neuroinflammation in rats with autism].

OBJECTIVES: To investigate the ameliorative effect of acupuncture at "Neiguan" (PC6) on behavioral deficits, hippocampal neuronal damage, an … uncture (ASD+sham-Acu), acupuncture (ASD+Acu), solvent (DMSO) control (ASD+DMSO), and positive drug bumetanide (ASD+Bu) groups (n=9 in each group). Manual acupuncture (uniform reinforcing-reducing manipulation) was applied to bilateral PC6 of newborn rats for 30 min, once daily, 6 d a week, for 15 d (from the 7th day to the 21st day after birth). After acupu …

Kir4.1 channels mediate a depolarization of hippocampal astrocytes under hyperammonemic conditions in situ.

Increased ammonium (NH(4) (+) ) concentration in the brain is the prime candidate responsible for hepatic encephalopathy (HE), a serious neurological disorder caused by liver failure and characterized by disturbed glutamatergic neurotransmission and impaired glial function. We investigated the mechanisms of NH(4) (+) -induced depolarization of astrocytes in mouse hippocampal slices using whole-cell patch-clamp and potassium-selective microelectrodes. At postnatal days (P) 18-21, perfusion with 5 mM NH(4) (+) evoked a transient increase in the extracellular potassium concentration ([K(+) ](o) )

Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

Glioblastoma (GB) is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+)-K(+)-Cl(-) cotransporter 1 (NKCC1) can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological

Roles of volume-sensitive chloride channel in excitotoxic neuronal injury.

Excitotoxicity is associated with stroke, brain trauma, and a number of neurodegenerative disorders. In the brain, during excitotoxic insults, neurons undergo rapid swelling in both the soma and dendrites. Focal swellings along the dendrites called varicosities are considered to be a hallmark of acute excitotoxic neuronal injury. However, it is not clear what pathway is involved in the neuronal anion flux that leads to the formation and resolution of excitotoxic varicosities. Here, we assessed the roles of the volume-sensitive outwardly rectifying (VSOR) Cl- channel in excitotoxic responses in

Tonic regulation of vascular tone by nitric oxide and chloride ions in rat isolated small coronary arteries.

We have investigated the involvement of Cl(-) in regulating vascular tone in rat isolated coronary arteries mounted on a small vessel myograph. Mechanical removal of the endothelium or inhibition of nitric oxide (NO) synthase with N(omega)-nitro-L-arginine methyl ester (L-NAME, 10(-4) M) led to contraction of rat coronary arteries, and these contractions were sensitive to nicardipine (10(-6) M). This suggests that release of NO tonically inhibits a contractile mechanism that involves voltage-dependent Ca(2+) channels. In arteries contracted with L-NAME, switching the bathing solution to physio

Analysis of the human guanylin gene and the processing and cellular localization of the peptide.

The complete cell biological analysis of human guanylin, a recently discovered regulatory peptide, is offered in this investigation: (i) the nucleotide sequence of the gene, (ii) the isolation and characterization of its circulating molecular form, and (iii) its localization in enterochromaffin cells of the gut. As determined by molecular cloning, DNA sequencing, and comparison with the known cDNA sequence, the approximately 2.6-kbp large gene consists of three exons interrupted by two introns. The putative promoter region contains a TTTAAAA sequence motif and several potential binding sites f

Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus.

PURPOSE: γ-Aminobutyric acid (GABA)ergic transmission plays an important role in the initiation of epileptic activity and the generation of ictal discharges. The functional alterations in the epileptiform hippocampus critically depend on GABAergic mechanisms and cation-chloride cotransporters. METHODS: To understand the cellular basis of specific functional alterations in the epileptic hippocampus, we studied physiologic characteristics and pharmacologically isolated evoked GABA(A) receptor-mediated inhibitory postsynaptic currents (IPSCs) recorded from principal neurons in hippocampal slices

Recurrent Pleural Effusions in an Elderly Female Patient With Renal Amyloidosis.

Amyloidosis is a rare and severe disease process that is often systemic in nature. Clinical presentations of patients include involvement of various organ systems such as the kidneys, heart, and lungs. As such, presentations of amyloidosis can be peculiar and can greatly mimic other conditions, making diagnosis very difficult. Delays in diagnosis or misdiagnoses can lead to significant morbidity and great potential for multi-organ dysfunctions. We describe the case of an elderly female patient without a known cardiac history who presented to the emergency department with increasing shortness o

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… Based on recommendations by nephrology, the patient was started on fluid restrictions, bumetanide 0.5 mg IV daily to treat the fluid overload state, and avoidance of non-steroidal anti-inflammatory drugs (NSAIDs) and other nephrotoxic medications. …

GABA(B) receptor activation mediates frequency-dependent plasticity of developing GABAergic synapses.

Activity-induced long-term modification of glutamatergic synapses depends on the frequency of synaptic activation. We found that long-term modification of developing rat hippocampal GABAergic synapses that was induced by repetitive coincident pre- and postsynaptic spiking was also frequency dependent. Spiking at 20-50 Hz resulted in synaptic potentiation, whereas spiking at 5 Hz led to synaptic depression. The potentiation was abolished by blocking GABA(B) receptors (GABA(B)Rs), whereas the depression was independent of GABA(B)R activation and could be converted to potentiation by elevating GA

In the adult hippocampus, chronic nerve growth factor deprivation shifts GABAergic signaling from the hyperpolarizing to the depolarizing direction.

GABA, the main inhibitory transmitter in adulthood, early in postnatal development exerts a depolarizing and excitatory action. This effect, which results from a high intracellular chloride concentration ([Cl(-)](i)), promotes neuronal growth and synaptogenesis. During the second postnatal week, the developmental regulated expression of the cation-chloride cotransporter KCC2 accounts for the shift of GABA from the depolarizing to the hyperpolarizing direction. Changes in chloride homeostasis associated with high [Cl(-)](i) have been found in several neurological disorders, including temporal l

Differences between cation-chloride co-transporter functions in the visual cortex of pigmented and albino rats.

Albinism in mammals is accompanied by specific morphological and functional alterations of the visual system. To understand their cellular basis we studied the physiological characteristics and transmembrane currents of pyramidal neurons in 350-microm-thick slices of visual cortex from pigmented and albino rats using whole-cell and gramicidin perforated patch-clamp recordings. The resting membrane potential was significantly more positive and the rheobase was significantly lower in neurons of layers II/III and V in albinos as compared with pigmented rats. No significant differences were found

Skeletal consequences of heart failure.

Heart failure (HF) is a prevalent clinical syndrome that causes significant physical limitations. Osteoporosis is also an important cause of loss of functionality, and it mainly affects women. There are several reports linking HF and osteoporosis, and both share risk factors. Most of the data available so far point to bone fragility as a consequence of HF, and several mechanisms have been identified to explain this relationship. Among the proposed pathophysiological mechanisms are the hyperactivation of the renin-angiotensin-aldosterone system and the increase in parathyroid hormone, functiona

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… Arch Intern Med 2009 ; 169 ( 2 ): 132 – 140 . 19171809 10.1001/archinternmed.2008.526 47 Rejnmark L Vestergaard P Heickendorff L , et al Loop diuretics increase bone turnover and decrease BMD in osteopenic postmenopausal women: results from a randomized controlled study with bumetanide . …

Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain.

Severe head trauma causes widespread neuronal shear injuries and acute seizures. Shearing of neural processes might contribute to seizures by disrupting the transmembrane ion gradients that subserve normal synaptic signaling. To test this possibility, we investigated changes in intracellular chloride concentration ([Cl(-)](i)) associated with the widespread neural shear injury induced during preparation of acute brain slices. In hippocampal slices and intact hippocampal preparations from immature CLM-1 mice, increases in [Cl(-)](i) correlated with disruption of neural processes and biomarkers