ABSTRACT
BACKGROUND: Drug-induced hypocarnitinemia has been noted as a cause of hypoglycemia in children. However, adult cases are extremely rare and pre-existing conditions (including endocrine disorders and frailty) have been suggested to be involved. Hypoglycemia due to drug-induced hypocarnitinemia is quite rare, and there were few reports of pivoxil-containing cephalosporin (PCC)-induced hypocarnitinemia in adults. CASE PRESENTATION: We present a case of an 87-year-old man with malnutrition, and frailty. He developed severe hypoglycemia with unconsciousness after taking cefcapene pivoxil hydrochloride, one of PCC, and hypocarnitinemia was diagnosed. Despite levocarnitine administration, asymptomatic mild hypoglycemia had persisted. Subsequent investigation revealed subclinical ACTH deficiency due to empty sella, which played a key role to maintain mild hypoglycemia as underlying disorder, and PCC-induced hypocarnitinemia triggered severe hypoglycemia. The patient responded to hydrocortisone therapy. CONCLUSIONS: We need to be aware of the facts that PCC can induce severe hypocarnitinemic hypoglycemia in elderly adults associated with frailty, malnutrition, and subclinical ACTH syndrome.
Subject(s)
Frailty , Hypoglycemia , Malnutrition , Adult , Child , Aged , Male , Humans , Aged, 80 and over , Cephalosporins , Monobactams , Adrenocorticotropic HormoneABSTRACT
Obinutuzumab is a novel glycoengineered, type-II anti-CD20 monoclonal antibody that was recently developed to treat follicular lymphoma (FL), the most prevalent subtype of indolent B-cell lymphoma. Several intensely hypermetabolic lesions (SUVmax: 40) were identified in the post-mediastinal and paraaortic lymph nodes by 18F-FDG-PET maximum-intensity projection images of a 58-year-old man who presented with systemic lymphadenopathy. A biopsy at the time of laparotomy definitively diagnosed grade 1 FL. The patient was given the recommended standard premedication, comprising acetaminophen (1000 mg), diphenhydramine (50 mg), and dexamethasone (20 mg), and then started on six cycles of obinutuzumab plus cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP). However, the patient developed severe hypotension and dyspnea about 15 min after starting obinutuzumab. It was difficult to differentiate between a possible allergic reaction and infusion-related reaction. A pleural effusion was drained to reduce the tumor burden, after which a single course of CHOP was started. Rituximab (R) was added 10 days later without incident, and the patient completed six cycles of the R-CHOP therapy without adverse events. We conclude that R-CHOP was safe for administration to patients who react to infused obinutuzumab. Such patients should be carefully monitored during R infusion, given the risk of cross-reactivity.
Subject(s)
Antibodies, Monoclonal, Humanized/adverse effects , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Lymphoma, Follicular/drug therapy , Rituximab/administration & dosage , Administration, Oral , Antibodies, Monoclonal, Humanized/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/administration & dosage , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Cyclophosphamide/administration & dosage , Doxorubicin/administration & dosage , Humans , Infusions, Intravenous/adverse effects , Lymphoma, Follicular/diagnostic imaging , Male , Middle Aged , Positron-Emission Tomography , Prednisone/administration & dosage , Self Administration , Treatment Outcome , Vincristine/administration & dosageABSTRACT
It is recognized that Wnt3a affects bone metabolism via the canonical Wnt/ß-catenin signalling pathway. We have previously shown that transforming growth factor-ß (TGF-ß) stimulates the synthesis of vascular endothelial growth factor (VEGF) via p44/p42 mitogen-activated protein (MAP) kinase, stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) and p38 MAP kinase in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the effect of Wnt3a on TGF-ß-stimulated VEGF synthesis in these cells. Wnt3a, which alone had little effect on the VEGF levels, significantly enhanced the TGF-ß-stimulated VEGF release. Lithium chloride and SB216763, inhibitors of glycogen synthase kinase 3ß, markedly amplified the TGF-ß-stimulated VEGF release. Wnt3a failed to affect the TGF-ß-induced phosphorylation of Smad2, p44/p42 MAP kinase, p38 MAP kinase or SAPK/JNK. Wnt3a and lithium chloride strengthened the VEGF mRNA expression induced by TGF-ß. These results strongly suggest that Wnt3a upregulates VEGF synthesis stimulated by TGF-ß via activation of the canonical pathway in osteoblasts.
Subject(s)
Osteoblasts/metabolism , Transforming Growth Factor beta/metabolism , Vascular Endothelial Growth Factor A/biosynthesis , Wnt Proteins/metabolism , Animals , Cell Line , Enzyme Inhibitors/pharmacology , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Glycogen Synthase Kinase 3 beta , Indoles/pharmacology , Lithium Chloride/pharmacology , MAP Kinase Kinase 4/drug effects , MAP Kinase Kinase 4/metabolism , Maleimides/pharmacology , Mice , Mitogen-Activated Protein Kinase 3/drug effects , Mitogen-Activated Protein Kinase 3/metabolism , Osteoblasts/drug effects , Phosphorylation/drug effects , RNA, Messenger , Signal Transduction , Smad2 Protein/drug effects , Smad2 Protein/metabolism , Transforming Growth Factor beta/pharmacology , Up-Regulation , Vascular Endothelial Growth Factor A/drug effects , Vascular Endothelial Growth Factor A/genetics , Wnt Proteins/pharmacology , Wnt3 Protein , Wnt3A Protein , beta Catenin/metabolism , p38 Mitogen-Activated Protein Kinases/drug effects , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
AMP-activated protein kinase (AMPK) is recognized as a regulator of energy homeostasis. We have previously reported that basic fibroblast growth factor (FGF-2) stimulates vascular endothelial growth factor (VEGF) release through the activation of p44/p42 mitogen-activated protein (MAP) kinase and stress-activated protein kinase/c-Jun N-terminal kinase (SAPK/JNK) in osteoblast-like MC3T3-E1 cells. In the present study, we investigated the involvement of AMPK in FGF-2-stimulated VEGF release in these cells. FGF-2 time-dependently induced the phosphorylation of AMPK α-subunit (Thr-172). Compound C, an AMPK inhibitor, which suppressed the FGF-2-induced phosphorylation of AMPK, significantly inhibited the VEGF release stimulated by FGF-2. The AMPK inhibitor also reduced the mRNA expression of VEGF induced by FGF-2. The FGF-2-induced phosphorylation of both p44/p42 MAP kinase and SAPK/JNK was attenuated by compound C. These results strongly suggest that AMPK positively regulates the FGF-2-stimulated VEGF synthesis via p44/p42 MAP kinase and SAPK/JNK in osteoblasts.
