Biomedical subjects

G Blanco

Publications and source records attributed to G Blanco.

At least 37 records · Page 2Linked to original sources

PubMed2001

Orbital intradiploic giant epidermoid cyst.

We report a case of an intradiploic epidermoid cyst of the lateral orbital wall that resulted in proptosis and downward displacement of the left eye. Computed tomography and magnetic resonance imaging revealed a bone-destroying mass involving the frontal, sphenoid, and zygomatic bones that extended into the orbit, temporalis, and anterior cranial fossa. Complete surgical removal was performed through a lateral orbitotomy. The lateral wall was reconstructed with a porous polyethylene sheet. The cyst has not recurred after 18 months of follow-up.

Adult↗

PubMed2001

c-erbB-2 positivity is a factor for poor prognosis in breast cancer and poor response to hormonal or chemotherapy treatment in advanced disease.

The aim of this work was to evaluate the prognostic and predictive values of c-erbB-2 in breast cancer. 650 patients were enrolled. The amplification/overexpression of c-erbB-2 from fresh frozen or paraffin-embedded breast tumour tissue samples was analysed by polymerase chain reaction (PCR) technique (75%), immunohistochemically (17%) or by Southern blot analysis (8%). 126 patients (19%) were positive for c-erbB-2. 148 patients developed metastatic disease, but only 35 were positive for c-erbB-2. Positivity for c-erbB-2 was significantly associated with node positivity, large tumour size, high grade of malignancy, low receptor status, postmenopausal status, and with a shorter overall survival. In multivariate regression analysis, only tumour size and nodal involvement were risk factors for poor survival when analysed separately together with c-erbB-2 and receptor status. Metastatic patients with c-erbB-2 positivity had a significantly shorter survival and disease-free survival (DFS) than the c-erbB-2-negative patients. 29 advanced patients with c-erbB-2 positivity showed a poor response rate to hormonal, non-anthracycline-based and anthracycline-based therapies. Positivity for the c-erbB-2 is a poor prognostic factor in breast cancer, but it also emerges as predictive of the response to hormonal or chemotherapy treatment once the disease has recurred.

Antineoplastic Agents, Hormonal↗

PubMed2001

Identification of a sugar flexible glycosyltransferase from Streptomyces olivaceus, the producer of the antitumor polyketide elloramycin.

BACKGROUND: Elloramycin is an anthracycline-like antitumor drug related to tetracenomycin C which is produced by Streptomyces olivaceus Tü2353. Structurally is a tetracyclic aromatic polyketide derived from the condensation of 10 acetate units. Its chromophoric aglycon is glycosylated with a permethylated L-rhamnose moiety at the C-8 hydroxy group. Only limited information is available about the genes involved in the biosynthesis of elloramycin. From a library of chromosomal DNA from S. olivaceus, a cosmid (16F4) was isolated that contains part of the elloramycin gene cluster and when expressed in Streptomyces lividans resulted in the production of a non-glycosylated intermediate in elloramycin biosynthesis, 8-demethyl-tetracenomycin C (8-DMTC). RESULTS: The expression of cosmid 16F4 in several producers of glycosylated antibiotics has been shown to produce tetracenomycin derivatives containing different 6-deoxysugars. Different experimental approaches showed that the glycosyltransferase gene involved in these glycosylation events was located in 16F4. Using degenerated oligoprimers derived from conserved amino acid sequences in glycosyltransferases, the gene encoding this sugar flexible glycosyltransferase (elmGT) has been identified. After expression of elmGT in Streptomyces albus under the control of the erythromycin resistance promoter, ermEp, it was shown that elmG can transfer different monosaccharides (both L- and D-sugars) and a disaccharide to 8-DMTC. Formation of a diolivosyl derivative in the mithramycin producer Streptomyces argillaceus was found to require the cooperative action of two mithramycin glycosyltransferases (MtmGI and MtmGII) responsible for the formation of the diolivosyl disaccharide, which is then transferred by ElmGT to 8-DMTC. CONCLUSIONS: The ElmGT glycosyltransferase from S. olivaceus Tü2353 can transfer different sugars into the aglycon 8-DMTC. In addition to its natural sugar substrate L-rhamnose, ElmGT can transfer several L- and D-sugars and also a diolivosyl disaccharide into the aglycon 8-DMTC. ElmGT is an example of sugar flexible glycosyltransferase and can represent an important tool for combinatorial biosynthesis.

Anthraquinones↗

PubMed2001

Fibreoptic nasal intubation in children with anticipated and unanticipated difficult intubation.

The establishment of a tracheal airway with direct laryngoscopy can be either a very difficult or an impossible task in children with congenital or acquired facial malformations. Out of 46 patients categorized as difficult tracheal intubation, fibreoptic laryngoscopy was used successfully in 44 children anaesthetized by mask with sevoflurane and oxygen or by an intravenous infusion of propofol and mask oxygenation. There were two failures (4.3%). One was due to excessive bleeding and secretions produced by the multiple attempts to intubate with direct laryngoscopy and the other failure in a patient with Pierre Robin syndrome and very small nasal passages that precluded the introduction of the endoscope. Fibreoptic laryngoscopy was successful in 37 cases (80.4%) on the first attempt to intubate and in seven (15.2%) on a second or third attempt. We conclude that fibreoptic laryngoscopy in anaesthetized children with difficult anticipated or unanticipated tracheal intubation in trained hands is a safe technique that can be lifesaving. Therefore, we urge all anaesthesia trainees to become proficient in fibreoptic tracheal intubation.

Adolescent↗

PubMed2001

The engineered, cytosolic form of human type I 3beta-hydroxysteroid dehydrogenase/isomerase: purification, characterization and crystallization.

Human type I 3beta-hydroxysteroid dehydrogenase/isomerase (3beta-HSD/isomerase) is an integral membrane protein of human placental trophoblast and of insect Sf9 cells transfected with recombinant baculovirus containing the cDNA encoding the enzyme. Purified native or wild-type enzyme remains in solution only in the presence of detergent that may prevent crystallization. The membrane-spanning domain (residues 283-310) of the enzyme protein was deleted in the cDNA using PCR-based mutagenesis. The modified enzyme was expressed by baculovirus in the cytosol instead of in the microsomes and mitochondria of the Sf9 cells. The cytosolic form of 3beta-HSD/isomerase was purified using affinity chromatography with Cibacron Blue 1000. The NAD(+) and NaCl used to elute the enzyme were removed by size-exclusion centrifugation. Hydroxylapatite chromatography yielded a 26-fold purification of the enzyme. SDS-PAGE revealed a single protein band for the purified cytosolic enzyme (monomeric molecular mass 38.8 kDa) that migrated just below the wild-type enzyme (monomeric molecular mass 42.0 kDa). Michaelis-Menten constants measured for 3beta-HSD substrate (dehydroepiandrosterone) utilization by the purified cytosolic enzyme (K(m)=4.5 microM, V(max)=53 nmol/min per mg) and the pure wild-type enzyme (K(m)=3.7 microM, V(max)=43 nmol/min per mg), for isomerase substrate (5-androstene-3,17-dione) conversion by the purified cytosolic (K(m)=25 microM, V(max)=576 nmol/min per mg) and wild-type (K(m)=28 microM, V(max)=598 nmol/min per mg) enzymes, and for NAD(+) reduction by the 3beta-HSD activities of the cytosolic (K(m)=35 microM, V(max)=51 nmol/min per mg) and wild-type (K(m)=34 microM, V(max)=46 nmol/min per mg) enzymes are nearly identical. The isomerase activity of the cytosolic enzyme requires allosteric activation by NADH (K(m)=4.6 microM, V(max)=538 nmol/min per mg) just like the wild-type enzyme (K(m)=4.6 microM, V(max)=536 nmol/min per mg). Crystals of the purified, cytosolic enzyme protein have been obtained. The inability to crystallize the detergent-solubilized, wild-type microsomal enzyme has been overcome by engineering a cytosolic form of this protein. Determining the tertiary structure of 3beta-HSD/isomerase will clarify the mechanistic roles of potentially critical amino acids (His(261), Tyr(253)) that have been identified in the primary structure.

Chromatography, Gel↗

PubMed2001

Effects of spatial and host variables on hematozoa in white-crowned sparrows wintering in Baja California.

A survey of blood parasites was conducted in February 1995 on white-crowned sparrows (Zonotrichia leucophrys) wintering in two environmentally different localities of Baja California Sur (Mexico). Blood parasite prevalence was higher in La Purísima (49%) than in San José del Cabo (8%), but there were no differences between ages or sexes within each locality. All haematozoa infections were by Haemoproteus coatneyi, except one bird in each site that were positive for Trypanosoma sp. We found no evidence for the predicted negative relationship between host body condition and intensity of parasitism. The relatively high prevalence in one site suggests that an increase of hematozoa transmission may occur in that area.

Animals↗

PubMed2001

[Usefulness of conjunctival biopsy as diagnostic technique].

PURPOSE: The conjuctival biopsy is described as a useful technique in the diagnosis of some chronic conjunctivitis, with low specific signs and with poor response to the conventional treatment. Furthermore it is quite important in the diagnosis of conjunctival diseases with potential dangerous treatment. PATIENTS AND METHODS: Three clinical cases are described. Case 1: A 37 years old woman with a chronic lesion of conjuctiva and the suspicion of blepharoconjunctivitis. There was no improvement with treatment. Case 2: A 58 years old woman with a chronic conjunctivitis and follicular reaction. Case 3: A 66 years old man who suffers from a cicatricial conjunctivis in both eyes with corneal lesion in one eye. A conjunctival biopsy was perfomed and studied under light microscopy and immunohistochemistry. There is a description of the technique. RESULTS: The results of every clinical case are described. In the first case the biopsy established the diagnosis of conjunctival lymphoma. In the second, the biopsy showed the appearance of granulomas and a diagnosis of conjunctival sarcoidosis was performed. In the third case a diagnosis of ocular cicatricial pemphigoid was established. CONCLUSION: Conjunctival biopsy is a useful and effective technique in the diagnosis of chronic conjunctivitis.

Adult↗

PubMed2001

Zymosan modulates CD44 isoform expression in a murine model of inflammation resembling rheumatoid arthritis synovitis.

OBJECTIVE: To study local inflammation induced by zymosan in the murine air pouch, considered a model of synovial-like tissue inflammation, we investigated the time-course synthesis of CD44 and tumor necrosis factor-alpha (TNF-alpha) mRNA and established a relationship with leukocyte migration into the air pouch and CD44 expression on the leukocyte membrane. METHODS: Leukocytes from the air pouch exudate were collected and counted at 1, 4, 12, 24, 48, and 72 h after zymosan or saline injection. CD44 and TNF-alpha mRNA were studied by RT-PCR. CD44 variable exon analysis was assessed by Southern blot and CD44 membrane expression by flow cytometry. RESULTS: Leukocyte accumulation after zymosan injection was significantly higher than in saline injected controls. CD44 standard and variable isoforms including at least variable exons v6 and v9 were highly expressed in leukocytes from the zymosan air pouch exudate. In contrast, only the CD44 mRNA standard isoform was present in leukocytes from saline air pouch. Maximal TNF-alpha mRNA level was observed at 48 h after zymosan injection, whereas CD44 mRNA was constantly expressed throughout the whole term of the experiment, although variations in leukocyte count and relative formula were observed. CONCLUSION: Expression of CD44 variable isoform in leukocytes was specifically induced by zymosan, since none was detected in saline controls. TNF-alpha mRNA expression and leukocyte count at every time point served as markers for local inflammation. The presence of variable isoforms, including at least exons v6 and v9, consistently expressed throughout the assay suggests that they could play a role in this arthritis-like inflammation induced under zymosan stimulus.

Animals↗

PubMed2001

[Anal and perianal lesions in Crohn's disease].

Crohn's disease is not a homogeneous clinical entity but may shows many clinical pictures during its period, prognosis and response to therapy. Anal and perianal localisations are frequently found; they can occur isolated, months or years in advance the disease, or can be concomitant with an ileal, colic or rectal involvement. There can be many kinds of lesions: simple, such as eczema or fissuration, complex, such as high rectal or rectovaginal fistulas. A rational classification of anal and perianal manifestations is suggested. Local medical therapy, is very effective in minor lesions, and has to be associated with systemic medical therapy particularly nowadays: the knowledge on phlogosis, biology and biotechnology revolution, have launched a new therapeutic era. Surgical therapy can be performed only in case of complex disease non responsive to medical therapy or when it is necessary to give a rest to anorectal tract. To perform a correct follow-up, considering unpredictability of lesions, a careful clinical evaluation and an intensive surveying plan associated with objective evaluation parameters are suggested.

Anus Diseases↗

PubMed2000

Safety and efficacy results of a randomized trial comparing adjuvant toremifene and tamoxifen in postmenopausal patients with node-positive breast cancer. Finnish Breast Cancer Group.

PURPOSE: In this multicenter trial, toremifene 40 mg/d was compared with tamoxifen 20 mg/d, both given orally for 3 years to postmenopausal, axillary node-positive women after breast surgery. PATIENTS AND METHODS: The first 899 patients (toremifene, n = 459; tamoxifen, n = 440) of the total of 1,480 patients accrued to the trial were included in this scheduled safety analysis. The mean follow-up time was 3.4 years. RESULTS: The two treatment groups were well balanced with respect to patient and disease characteristics. The subjective side-effect profile was similar in both treatment groups. Slightly more vascular complications (deep vein thromboses, cerebrovascular events, and pulmonary embolisms) were seen among tamoxifen-treated patients (5.9%) as compared with toremifene-treated patients (3.5%) (P: =.11), whereas bone fractures (P: =.09) and vaginal leukorrhea (P: =.05) were more common in the toremifene group. The number of subsequent second cancers was similar. The breast cancer recurrence rate was 23.1% (n = 106) in the toremifene group and 26.1% (n = 115) in the tamoxifen group (P: =.31). When only patients with estrogen receptor (ER)-positive cancer were considered (n = 556), the risk for breast cancer recurrence was nonsignificantly lower among the toremifene-treated women, with a hazards ratio of 0.74 (90% confidence interval, 0.52 to 1.04; P: =.14). The mean time to breast cancer recurrence and overall survival were similar in both groups. CONCLUSION: The side-effect profile of toremifene resembles that of tamoxifen. The efficacy of toremifene seems to be no less than that of tamoxifen. The trend for fewer breast cancer recurrences in the ER-positive subgroup is encouraging, but a longer follow-up is needed to confirm this.

Antineoplastic Agents, Hormonal↗

PubMed2000

Expression, activity and distribution of Na,K-ATPase subunits during in vitro neuronal induction.

The expression pattern of the alpha and beta isoforms and the gamma subunit of the Na,K-ATPase was investigated during in vitro induction of pluripotent murine embryonic stem (ES) cells into neuronal cells. alpha1 protein was expressed in undifferentiated ES (UES) cells and throughout all stages studied. In contrast, alpha3 protein was prominent only when neuronal cells have reached full differentiation. In this model, neuron-depleted cultures did not express the alpha3 isoform, indicating its specificity for mature neuronal cells. UES possessed Na,K-ATPase activity consistent with a single isoform (alpha1), whereas in fully mature neuronal cells a ouabain-sensitive isoform (alpha3) accounted for 27+/-4% of the activity, and a ouabain-resistant isoform (alpha1) 66+/-3%. Immunocytochemistry of mature neuronal cells for alpha1 and alpha3 proteins showed a similar distribution, including cell soma and processes, without evidence of polarization. beta1 protein was expressed in uninduced ES, embryonic bodies (EB) and neuronal cells. While proteins of the beta2 and beta3 isoforms were not detected by immunoblots (except for beta2 in UES), their mRNAs were detected in UES and EB (beta2 and beta3), and in immature and fully differentiated neuronal cells (beta3). Message for the beta2 isoform, however, was not present in neuronal cells. gamma subunit mRNA and protein were undetectable at any stage. These results provide further characterization of neuron-like cells obtained by induction of ES cells in vitro, and establish a model for the expression of isoforms of the Na,K-ATPase during neuronal differentiation. The relation to other aspects of neuronal cell development and relevance to a specialised function for the alpha3 subunit in neurons are discussed.

Animals↗

PubMed2000

Characterization of two glycosyltransferases involved in early glycosylation steps during biosynthesis of the antitumor polyketide mithramycin by Streptomyces argillaceus.

A 2,580-bp region of the chromosome of Streptomyces argillaceus, the producer of the antitumor polyketide mithramycin, was sequenced. Analysis of the nucleotide sequence revealed the presence of two genes (mtmGIII and mtmGIV) encoding proteins that showed a high degree of similarity to glycosyltransferases involved in the biosynthesis of various antibiotics and antitumor drugs. Independent insertional inactivation of both genes produced mutants that did not synthesize mithramycin but accumulated several mithramycin intermediates. Both mutants accumulated premithramycinone, a non-glycosylated intermediate in mithramycin biosynthesis. The mutant affected in the mtmGIII gene also accumulated premithramycin A1, which contains premithramycinone as the aglycon unit and a D-olivose attached at C-12a-O. These experiments demonstrate that the glycosyltransferases MtmGIV and MtmGIII catalyze the first two glycosylation steps in mithramycin biosynthesis. A model is proposed for the glycosylation steps in mithramycin biosynthesis.

Amino Acid Sequence↗

PubMed2000

Extramedullary plasmacytoma of the orbit.

PURPOSE: To report a case of extramedullary plasmacytoma of the orbit. METHODS: A 71-year-old patient presented with diplopia eyelid fullness and limitation of ocular motility in the left eye. Visual acuity was counting fingers, intraocular pressure 34 mmHg and fundus eye examination showed choroidal folds in the involved eye. RESULTS: CT scan showed a mass filling the superior and external left orbit without bone destruction. A biopsy was performed revealing that the tumour was composed of plasmacytoid cells positive with immunohistochemical stains for Kappa light chains and epithelial membrane antigen. Systemic work up was negative. The diagnosis of extramedullary orbital plasmacytoma was made. The patient was treated with external beam radiotherapy (40 Gy) and has remained disease free for four years (49 months). CONCLUSION: Extramedullary plasmacytomas of the orbit are extremely rare tumours. Accurate and early diagnosis is essential for the therapeutic approach. Extensive medical work up to rule out multiple myeloma or other malignant lymphoproliferative conditions involving the orbit is needed when the diagnosis of orbital extramedullary plasmacytoma is suspected because treatment and prognosis are very different.

Aged↗

PubMed2000

The alpha4 isoform of the Na,K-ATPase is expressed in the germ cells of the testes.

In addition to the three isoforms of the catalytic subunit of the Na, K-ATPase originally identified (alpha1, alpha2, and alpha3), a fourth alpha polypeptide (alpha4) has recently been found in mammalian cells. This novel alpha-subunit of the Na,K-ATPase is selectively expressed in male gonadal tissues. In the testes, alpha4 is functionally active and comprises approximately half of the Na, K-ATPase activity of the organ. At present, the pattern of expression of the alpha4 polypeptide within the cells of the male gonad is unknown. By in situ hybridization, immunocytochemistry, and the ouabain inhibition profile of Na,K-ATPase activity, we show that the alpha4-subunit is expressed in the germ cells of rat testes. The highest amounts of the isoform are found in spermatozoa, where it constitutes two thirds of the Na,K-ATPase activity of the gametes. The other Na pump present in the cells is the ubiquitously expressed alpha1 polypeptide. The characteristic localization of alpha4 in the gonad is further supported by the drastic reduction of the polypeptide in mice that are infertile as a consequence of arrest in maturation of the germ cells. In addition, GC-1spg cells, a murine cell line derived from testis spermatogonia, also contain the Na, K-ATPase alpha4 polypeptide. However, the level of expression of the isoform in these cells is much lower than in the spermatozoa, a fact that may depend on the limited ability of the GC-1spg cells to differentiate in vitro. The particular expression of the Na,K-ATPase alpha4 isoform we encounter and the specific enzymatic properties of the polypeptide suggests its importance for ionic homeostasis of the germ cells of the testes.

Animals↗

PubMed2000

Louse flies on birds of Baja California.

Louse flies were collected from 401 birds of 32 species captured in autumn of 1996 in Baja California Sur (Mexico). Only one louse fly species (Microlynchia pusilla) was found. It occurred in four of the 164 common ground doves (Columbina passerina) collected. This is a new a host species for this louse fly.

Animals↗

PubMed2000

Uveal melanoma model with metastasis in rabbits: effects of different doses of cyclosporine A.

OBJECTIVE: To compare the toxicity and efficacy of different doses of cyclosporine A (CsA) in a rabbit model of uveal melanoma. METHODS: We used four experimental groups: control, no CsA; group 1, 15 to 10 mg/kg/day; group 2, 15 mg/kg/day; and group 3, 20 mg/kg/day. The MKT-BR cell line was implanted in the choroid. All animals underwent ophthalmoscopic evaluation; the animals were weighed and blood levels of CsA, blood urea nitrogen (BUN), creatinine and alanine aminotransferase (ALT) were measured weekly. Necropsies and histologic study were performed to detect intraocular tumors and metastasis. RESULTS: A difference in survival rates was found between groups 2 and 3 (p = 0.0042). Differences were observed in the mean BUN and creatinine levels (p < 0.001 and p < 0.003, respectively) between groups but not in the ALT. Intraocular tumors were detected ophthalmoscopically in 50%, 65%, and 70% of the animals in groups 1, 2, and 3 respectively, and histologically in 70%, 90%, and 100% of the same groups. Lung metastases were found in 26.8% of animals with intraocular tumors. Differences were observed in mean CsA blood levels between animals with and without histologically demonstrated uveal tumors (p = 0.001) but not in animals with or without metastasis. CONCLUSIONS: Different doses of CsA affect survival, tumor development and renal toxicity. Metastatic disease is independent of CsA dose and the subsequent CsA blood levels. A blood level of CsA ranging from 500 to 1000 ng/ml and doses of 10 to 15 mg/kg/day may effectively develop this model of uveal melanoma.

Alanine Transaminase↗

PubMed2000

[Isoforms modulation of CD44 adhesion molecule in a murine model of ischemia and intestinal reperfusion].

Gut ischemia-reperfusion (G-IR) induces a systemic inflammatory response, in which leukocyte contribution to this injury in distant organs is important. ICAM-1 as well as CD11/CD18 have been involved in leukocyte infiltration in liver and lungs. CD44 adhesion molecule plays an essential role in other inflammatory processes such as rheumatoid arthritis and allergic contact dermatitis, however its implication in G-IR has not been described. In order to establish a possible role of CD44 in the development of systemic inflammation by G-IR, we have studied CD44 mRNA expression by RT-PCR in a murine model of gut ischemia reperfusion. Animals subjected to G-IR showed an increased number of CD44 variable isoforms expressed in liver and spleen compared to non-treated animals or animals subjected to laparotomy. This finding indicates that G-IR specifically induces the expression of different CD44 variable isoforms. Liver CD44 upregulation in animals subjected to G-IR suggests a contribution of this molecule to lymphocyte activation and migration to this injured organ. Moreover, increased isoform expression in spleen may be induced by the proinflammatory environment resulting from a systemic depuration activity.

Adjuvants, Immunologic↗

PubMed1999

Functional characterization of a testes-specific alpha-subunit isoform of the sodium/potassium adenosinetriphosphatase.

Different isoforms of the sodium/potassium adenosinetriphosphatase (Na,K-ATPase) alpha and beta subunits have been identified in mammals. The association of the various alpha and beta polypeptides results in distinct Na,K-ATPase isozymes with unique enzymatic properties. We studied the function of the Na,K-ATPase alpha4 isoform in Sf-9 cells using recombinant baculoviruses. When alpha4 and the Na pump beta1 subunit are coexpressed in the cells, Na, K-ATPase activity is induced. This activity is reflected by a ouabain-sensitive hydrolysis of ATP, by a Na(+)-dependent, K(+)-sensitive, and ouabain-inhibitable phosphorylation from ATP, and by the ouabain-inhibitable transport of K(+). Furthermore, the activity of alpha4 is inhibited by the P-type ATPase blocker vanadate but not by compounds that inhibit the sarcoplasmic reticulum Ca-ATPase or the gastric H,K-ATPase. The Na,K-ATPase alpha4 isoform is specifically expressed in the testis of the rat. The gonad also expresses the beta1 and beta3 subunits. In insect cells, the alpha4 polypeptide is able to form active complexes with either of these subunits. Characterization of the enzymatic properties of the alpha4beta1 and alpha4beta3 isozymes indicates that both Na,K-ATPases have similar kinetics to Na(+), K(+), ATP, and ouabain. The enzymatic properties of alpha4beta1 and alpha4beta3 are, however, distinct from the other Na pump isozymes. A Na, K-ATPase activity with similar properties as the alpha4-containing enzymes was found in rat testis. This Na,K-ATPase activity represents approximately 55% of the total enzyme of the gonad. These results show that the alpha4 polypeptide is a functional isoform of the Na,K-ATPase both in vitro and in the native tissue.

Adenosine Triphosphate↗