BACKGROUND: The SARS-CoV-2 omicron variant produces more symptoms in the upper respiratory tract than in the lower respiratory tract. This form of "common cold" can cause inflammation of the oropharynx and the Eustachian tube, leading to the multiplication of bacteria such as Streptococcus pneumoniae in the oropharynx. Eustachian tube dysfunction facilitates migration of these bacteria to the middle ear, causing inflammation and infection (otitis media), which in turn could lead to further complications such as acute mastoiditis and meningitis. CASE PRESENTATION: In January 2022, during the rapid spread of the omicron variant of the SARS-CoV-2 virus, two patients presented to the emergency room at our hospital complaining of headache and a low level of consciousness. A few days prior to admission, the patients had been diagnosed with COVID-19 based on clinical manifestations of a cold virus, without respiratory failure. Cranial computed tomography revealed signs of bilateral invasion of the middle ear in both cases. Lumbar puncture was compatible with acute bacterial meningitis, and S. pneumoniae was isolated in cerebrospinal fluid in both patients. RT-PCR tests for SARS-CoV-2 were repeated, confirming the presence of the omicron variant in one of the patients. We were unable to confirm the variant in the second patient due to the low viral load in the nasopharyngeal sample obtained at admission. However, the time of diagnosis (i.e., during the peak spread of the omicron variant), strongly suggest the presence of the omicron variant. Both patients were admitted to the intensive care unit and both showed rapid clinical improvement after initiation of antibiotic treatment. CONCLUSIONS: The omicron variant of the SARS-CoV-2 virus can promote the development of otitis media and secondary acute bacterial meningitis. S. pneumoniae is one of the main bacteria involved in this process.
Langerhans cell histiocytosis is a systemic disease associated with the proliferation of this type of cells in tissues. Its prevalence is estimated at 1-9/100 000. Bone is the most frequently affected organ, followed by the skin, lymph nodes, haematopoietic system, pituitary gland, lungs and liver. In the majority of cases, onset occurs during childhood, with peak between one and three years of age, and poor prognosis before two years of age. The haematological forms (pancytopenia) are usually aggressive in infants. We report a case of Langerhans cell histiocytosis with neonatal onset and complex diagnosis: maintained and significant leukocytosis was the predominant data for the first two months of life, so some type of leukemia was considered. However, the most common blood disorder in Langerhans cell histiocytosis is pancytopenia rather than leukocytosis, so that the diagnosis was delayed.
La histiocitosis de células de Langerhans es una enfermedad sistemica asociada con la proliferación de este tipo de células en distintos tejidos. La prevalencia estimada es de 1-9/100 000. El órgano más frecuentemente afectado es el hueso, seguido por la piel, ganglios linfáticos, sistema hematopoyético, hipófisis, pulmones e hígado. En la mayoría de los casos, la enfermedad debuta en la infancia, con pico entre uno y tres años de edad, y tiene mal pronóstico cuando ocurre antes de los dos años. La afectación del sistema hematopoyético, manifestada en forma de pancitopenia, suele ser agresiva en los lactantes. Se presenta un caso de histiocitosis de células de Langerhans con debut neonatal y complejo diagnóstico, ya que, los dos primeros meses de vida, el dato predominante era una leucocitosis importante mantenida que obligaba a descartar alguna forma de leucemia, mientras que la alteración hematológica más frecuente en la histiocitosis de células de Langerhans, como se ha comentado, es la pancitopenia, lo que motivó un retraso en el diagnóstico.
Histiocytosis, Langerhans-Cell/diagnosis , Age of Onset , Humans , Infant, Newborn
La histiocitosis de células de Langerhans es una enfermedad sistemica asociada con la proliferación de este tipo de células en distintos tejidos. La prevalencia estimada es de 1-9/100 000. El órgano más frecuentemente afectado es el hueso, seguido por la piel, ganglios linfáticos, sistema hematopoyético, hipófisis, pulmones e hígado. En la mayoría de los casos, la enfermedad debuta en la infancia, con pico entre uno y tres años de edad, y tiene mal pronóstico cuando ocurre antes de los dos años. La afectación del sistema hematopoyético, manifestada en forma de pancitopenia, suele ser agresiva en los lactantes. Se presenta un caso de histiocitosis de células de Langerhans con debut neonatal y complejo diagnóstico, ya que, los dos primeros meses de vida, el dato predominante era una leucocitosis importante mantenida que obligaba a descartar alguna forma de leucemia, mientras que la alteración hematológica más frecuente en la histiocitosis de células de Langerhans, como se ha comentado, es la pancitopenia, lo que motivó un retraso en el diagnóstico.
Langerhans cell histiocytosis is a systemic disease associated with the proliferation of this type of cells in tissues. Its prevalence is estimated at 1-9/100 000. Bone is the most frequently affected organ, followed by the skin, lymph nodes, haematopoietic system, pituitary gland, lungs and liver. In the majority of cases, onset occurs during childhood, with peak between one and three years of age, and poor prognosis before two years of age. The haematological forms (pancytopenia) are usually aggressive in infants. We report a case of Langerhans cell histiocytosis with neonatal onset and complex diagnosis: maintained and significant leukocytosis was the predominant data for the first two months of life, so some type of leukemia was considered. However, the most common blood disorder in Langerhans cell histiocytosis is pancytopenia rather than leukocytosis, so that the diagnosis was delayed.
Humans , Infant, Newborn , Histiocytosis, Langerhans-Cell/diagnosis , Age of Onset
Antineoplastic Agents, Phytogenic/therapeutic use , Facial Neoplasms/drug therapy , Hemangioendothelioma/drug therapy , Kasabach-Merritt Syndrome/drug therapy , Purinergic P2Y Receptor Antagonists/therapeutic use , Sarcoma, Kaposi/drug therapy , Ticlopidine/therapeutic use , Vincristine/therapeutic use , Facial Neoplasms/pathology , Hemangioendothelioma/pathology , Humans , Infant, Newborn , Kasabach-Merritt Syndrome/pathology , Male , Sarcoma, Kaposi/pathology , Treatment Outcome
We present the fulminant case of a neonate whose symptoms, lesions, imaging, and laboratory tests perfectly simulated a neonatal neuroblastoma and the definitive diagnosis was finally given by necropsy as follows: Infantile hepatic hemangioendothelioma type 2 with extrahepatic extension affecting skin, lung, intestine, suprarenal, and soft tissue.
Hemangioendothelioma , Infant, Newborn, Diseases , Liver Neoplasms , Neuroblastoma , Skin Neoplasms/pathology , Soft Tissue Neoplasms/pathology , Viscera/pathology , Autopsy , Fatal Outcome , Female , Hemangioendothelioma/diagnosis , Hemangioendothelioma/pathology , Humans , Infant, Newborn , Infant, Newborn, Diseases/diagnosis , Infant, Newborn, Diseases/pathology , Liver Neoplasms/diagnosis , Liver Neoplasms/pathology , Male , Neuroblastoma/diagnosis , Neuroblastoma/pathology , Soft Tissue Neoplasms/diagnosis
The X-ray crystal structure of the vanadium bromoperoxidase from the red algae Corallina pilulifera has been solved in the presence of the known substrates, phenol red and phloroglucinol. A putative substrate binding site has been observed in the active site channel of the enzyme. In addition bromide has been soaked into the crystals and it has been shown to bind unambiguously within the enzyme active site by using the technique of single anomalous dispersion. A specific leucine amino acid is seen to move towards the bromide ion in the wild-type enzyme to produce a hydrophobic environment within the active site. A mutant of the enzyme where arginine 397 has been changed to tryptophan, shows a different behaviour on bromide binding. These results have increased our understanding of the mechanism of the vanadium bromoperoxidases and have demonstrated that the substrate and bromide are specifically bound to the enzyme active site.
Peroxidases/chemistry , Rhodophyta/enzymology , Vanadium/chemistry , Binding Sites , Catalytic Domain , Crystallography, X-Ray , Kinetics , Models, Molecular , Peroxidases/metabolism , Protein Conformation , Substrate Specificity , Vanadium/metabolism
The Fasciola hepatica thioredoxin protein structure has been determined to 1.45A resolution. This is the first example of a single crystal structure to show the active site cysteine residues in both the reduced and disulfide oxidised form. Consistent with this observation the process of oxidation appears to require very little rearrangement of the surrounding protein structure. The F. hepatica thioredoxin structure has been compared to other thioredoxin protein structures already known and is found to be highly conserved. The F. hepatica protein is most similar to that of the thioredoxin from its human and animal hosts but it resembles other parasitic thioredoxins with regard to having no additional cysteine residues and is therefore not regulated by transient disulfide bond formation as proposed for thioredoxins from higher eukaryotic species.
Fasciola hepatica/chemistry , Helminth Proteins/chemistry , Thioredoxins/chemistry , Amino Acid Sequence , Animals , Binding Sites , Conserved Sequence , Crystallography, X-Ray , Humans , Models, Molecular , Molecular Sequence Data , Protein Structure, Tertiary , Sequence Alignment
Bromoperoxidase from the macro-alga Corallina pilulifera is an enzyme that possesses vanadate in the catalytic center, and shows a significant thermostability and stability toward organic solvents. The structural analysis of the recombinant enzyme overexpressed in yeast revealed that it contains one calcium atom per subunit. This has been confirmed by inductively coupled plasma emission spectrometry experiments. The study of the effect of metal ions on the apo-enzyme stability has shown that the calcium ion significantly increased the enzyme stability. In addition, vanadate also increased the thermostability and strontium and magnesium ions had similar effects as calcium. The holo-enzyme shows high stability in a range of organic solvents. The effect of the different ions and solvents on the structure of the enzyme has been studied by circular dichroism experiments. The high stability of the enzyme in the presence of organic solvents is useful for its application as a biocatalyst.
Calcium/pharmacology , Peroxidases/metabolism , Rhodophyta/enzymology , Vanadium/pharmacology , Amino Acid Sequence , Apoenzymes/metabolism , Calcium/chemistry , Circular Dichroism , Enzyme Stability/drug effects , Ions/pharmacology , Models, Molecular , Molecular Sequence Data , Molybdenum/pharmacology , Protein Structure, Quaternary , Protein Subunits/chemistry , Protein Subunits/metabolism , Sequence Alignment , Solvents/chemistry , Solvents/pharmacology , Temperature , Tungsten Compounds/pharmacology , Vanadium/chemistry
The halide specificity of vanadium-dependent bromoperoxidase (BPO) from the marine algae, Corallina pilulifera, has been changed by a single amino acid substitution. The residue R397 has been substituted by the other 19 amino acids. The mutant enzymes R397W and R397F showed significant chloroperoxidase (CPO) activity as well as BPO activity. These mutant enzymes were purified and their properties were investigated. The maximal velocities of CPO activities of the R397W and R397F enzymes were 31.2 and 39.2 units/mg, and the K(m) values for Cl(-) were 780 mM and 670 mM, respectively. Unlike the native enzyme, both mutant enzymes were inhibited by NaN(3). In the case of the R397W enzyme, the incorporation rate of vanadate into the active site was low, compared with the R397F and the wild-type enzyme. These results supported the existence of a specific halogen binding site within the catalytic cleft of vanadium haloperoxidases.
Eukaryota/enzymology , Halogens/metabolism , Peroxidases/chemistry , Peroxidases/metabolism , Protein Engineering , Vanadium/metabolism , Binding Sites , Escherichia coli/genetics , Eukaryota/genetics , Genetic Vectors/genetics , Kinetics , Models, Molecular , Mutation/genetics , Peroxidases/genetics , Peroxidases/isolation & purification , Protein Structure, Tertiary , Recombinant Proteins/antagonists & inhibitors , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Recombinant Proteins/metabolism , Saccharomyces cerevisiae/genetics , Substrate Specificity
The crystallographic structures of both the vanadium chloroperoxidase and bromoperoxidase enzymes have been determined with either vanadium or phosphate bound at their active site. The amino acids that are involved in phosphate binding in the acid phosphatase enzymes and those that are coordinated to vanadium in the haloperoxidases appear to be conserved between the two classes of enzyme. The detailed active site architecture for enzymes that recognize and use either vanadium or phosphate will be discussed in relation to their proposed enzymatic mechanism.
Acid Phosphatase/chemistry , Acid Phosphatase/metabolism , Chloride Peroxidase/chemistry , Chloride Peroxidase/metabolism , Peroxidases/chemistry , Peroxidases/metabolism , Acid Phosphatase/genetics , Amino Acid Sequence , Catalytic Domain , Chloride Peroxidase/genetics , Models, Molecular , Molecular Sequence Data , Mutagenesis, Site-Directed , Peroxidases/genetics , Phosphates/chemistry , Protein Conformation , Rhodophyta/enzymology , Rhodophyta/genetics , Sequence Homology, Amino Acid , Vanadium/chemistry
Molybdenum alkynyl complexes [Mo(C identical to CR)(eta 3-allyl)(CO)2(phen)] feature long Mo-Calkynyl bond distances and propensity to undergo the cleavage of these bonds, a property that allowed their use as acetylide transfer reagents.
Formation of polycyclic structures within a few minutes: The intramolecular cyclization of diynes, activated by a benzenesulfenyl substituent, upon reaction with IPy2 BF4 proceeds as an efficient exo-endo coupling. A subsequent novel Friedel-Crafts-like ring closure provides the product [Eq. (1)]. Thus, intra- and intermolecular cyclizations can be carried out.
